potential role in health and diseasea serine proteinase inhibitor in human articular...
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PROTEASES II Potential Role in Health and Disease
Edited by
Walter H. Hörl University of Freiburg
Freiburg, Federal Republic of Germany
and August Heidland University of Würzburg Würzburg, Federal Republic of Germany
PLENUM PRESS • NEW YORK AND LONDON
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Library of Congress Cataloging in Publication Data International Symposium on Proteases: Potential Role in Health and Disease (2nd: 1987: Rothenburg ob der Tauber, Germany)
Proteases II: potential role in health and disease. (Advances in experimental medicine and biology; v. 240) "Proceedings of the Second International Symposium on Proteases: Potential Role in
Health and Disease, held May 17-20, 1987 in Rothenburg ob der Tauber, Federal Republic of Germany"—T.p. verso.
Includes bibliographies and index. 1. Proteolytic enzymes —Congresses. 2. Proteolytic enzymes — Pathophysiology —
Congresses. 3. Proteolytic enzyme inhibitors — Congresses. I. Hörl, Walter H. II. Heidland, August. III. Title. IV. Series. [DNLM: 1. Peptide Hydrolases-congresses. 2. Protease Inhibitors-congresses. Wl AD559 v.240 / QU 136161 1987] QP609.P78I57 1987 612'.01516 88-25549 ISBN 0-306-43018-5
© 1988 Plenum Press, New York A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013 All rights reserved No part of this book may be reproduced, stored in a retrieval System, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher
Proceedings of the Second International Symposium on Proteases: Potential Role in Health and Disease, held May 17-20, 1987, in Rothenburg ob der Tauber, Federal Republic of Germany
Printed in the United States of America
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CONTENTS
I PHYSIOLOGY AND PATHOPHYSIOLOGY OF PROTEASES AND THEIR INHIBITORS
A s p a r t i c P r o t e i n a s e s and I n h i b i t o r s f o r t h e i r C o n t r o l i n H e a l t h and D i s e a s e 1
J . K a y , R. A. Jupp , C. G. N o r e y , A. D. R i c h a r d s , W. A. R e i d , R. T. T a g g a r t , I . M. S a m l o f f , and B. M. Dunn
Human N e u t r a l E n d o p e p t i d a s e 2 4 .11 (NEP, E n k e p h a l i n a s e ) ; F u n c t i o n , D i s t r i b u t i o n and R e l e a s e 13
E. G. Erdös and R. A. S k i d g e l
N e u t r o p h i l E l a s t a s e and C a t h e p s i n G: S t r u c t u r e , F u n c t i o n and B i o l o g i c a l C o n t r o l 23
W. W a t o r e k , D. F a r l e y , G. S a l v e s e n , and J . T r a v i s
The D e g r a d a t i o n o f C o l l a g e n by a M e t a l l o p r o t e i n a s e f r o m Human L e u c o c y t e s 33
U. K o h n e r t , R. O b e r h o f f , J . F e d r o w i t z , U. B e r g m a n n , J . R a u t e r b e r g , and H. T s c h e s c h e
P l a s m a Membrane P r o t e a s e s as U s e f u l T o o l i n H i s t o c h e m i c a l T o x i c o l o g y 45
R. G r a f and R. G o s s r a u
A c t i v a t i o n o f L e u k o c y t e s Düring P r o l o n g e d P h y s i c a l E x e r c i s e 57
K. K o k o t , R. M. S c h a e f e r , M. T e s c h n e r , U. G i l g e , R. P l a s s , and A. H e i d l a n d
I n h i b i t i o n o f Human N e u t r o p h i l E l a s t a s e by P o l y g u a n y l i c A c i d and o t h e r S y n t h e t i c P o l y n u c l e o t i d e s 65
S. S i m o n , M. V e r e d , A. R i n e h a r t , J . C h e r o n i s , and A. J a n o f f
I n h i b i t i o n o f Human N e u t r o p h i l E l a s t a s e by A c i d -S o l u b l e I n t e r - A l p h a - T r y p s i n I n h i b i t o r 75
A. G a s t and J . G. B i e . t h
D e v e l o p m e n t o f E g l i n c as a Drug : P h a r m a c o k i n e t i c s 83
H. P. N i c k , A. P r o b s t , and H. P. S c h n e b l i
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M o n o c l o n a l A n t i b o d i e s R e c o g n i z i n g I n t e r - A l p h a -T r y p s i n - I n h i b i t o r and i t s R e l a t e d F r a g m e n t s -E v i d e n c e f o r t h e I n v o l v e m e n t o f t h e P r o t e i n a s e I n h i b i t o r i n C u t a n e o u s ( P a t h o - ) P h y s i o l o g y 89
C. J u s t u s , K. H o c h s t r a s s e r , and M. D. Kr a m e r
I n h i b i t i o n o f Human C h y m o t r y p s i n - L i k e P r o t e a s e s by A l p h a - 1 - P r o t e i n a s e I n h i b i t o r and A l p h a - 1 -A n t i c h y m o t r y p s i n 97
A. Hayem, D. M a r k o , A. L a i n e , and M. D a v r i l
I m m u n o r e a c t i v e P a n c r e a t i c S e c r e t o r y T r y p s i n I n h i b i t o r i n G a s t r o i n t e s t i n a l M ucosa 101
M. Bohe, C. L i n d s t r ö m , and K. O h l s s o n
I I PROTEASES AND LUNG
S e m i s y n t h e t i c I n h i b i t o r s o f Human L e u k o c y t e E l a s t a s e and t h e i r P r o t e c t i v e E f f e c t on Lung E l a s t i n D e g r a d a t i o n i n v i t r o 107
J . Beckmann, A. M e h l i c h , H. R. W e n z e l , and H. T s c h e s c h e
Human B r o n c h i a l P r o t e i n a s e I n h i b i t o r - . R a p i d P u r i f i c a t i o n P r o c e d u r e and I n h i b i t i o n o f L e u c o c y t e E l a s t a s e i n P r e s e n c e and i n A b s e n c e o f Human Lung E l a s t i n 115
C. B o u d i e r , D. C a r v a l l o , M. B r u c h , C. R o i t s c h , M. C o u r t n e y , and J . G. B i e t h
F u n c t i o n a l S t u d i e s o f Human S e c r e t o r y L e u k o c y t e P r o t e a s e I n h i b i t o r 123
K. O h l s s o n , M. B e r g e n f e l d t , and P. Björk
The R o l e o f Chymase i n I o n o p h o r e - I n d u c e d H i s t a m i n e R e l e a s e f r o m Human P u l m o n a r y M a s t C e l l s 133
T. H u l t s c h , M. E n n i s , and H. H. H e i d t m a n n
P r o t e o l y t i c A c t i v i t i e s i n B r o n c h o a l v e o l a r L a v a g e F l u i d C o r r e l a t e t o S t a g e and C o u r s e o f I n t e r s t i t i a l Lung D i s e a s e 137
M. S c h m i d t and E. B r u g g e r
B e h a v i o u r o f A n g i o t e n s i n C o n v e r t i n g Enzyme, H y d r o x y p r o l i n e and some P r o t e a s e I n h i b i t o r s i n P u l m o n a r y S a r c o i d o s i s 145
M. M a s i a k , B. P o d w y s o c k i , and A. G a j e w s k a
E x p e r i m e n t a l S t u d i e s on t h e A d u l t R e s p i r a t o r y D i s t r e s s S y n drome: E l a s t a s e I n f u s i o n i n N o r m a l and A g r a n u l o c y t i c M i n i p i g s 149
H. B u r c h a r d i and T. S t o k k e
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I I I PROTEASES AND LIVER
A r g i n y l a t i o n , S u r f a c e H y d r o p h o b i c i t y and D e g r a d a t i o n o f C y t o s o l P r o t e i n s f r o m R a t H e p a t o c y t e s 159
P. B o h l e y , J . K o p i t z , and G. Adam
P r o t e i n a s e I n h i b i t o r s as A c u t e P h a s e R e a c t a n t s : R e g u l a t i o n o f S y n t h e s i s and T u r n o v e r 171
A. K o j , D. M a g i e l s k a - Z e r o , A. K u r d o w s k a , and J . B e r e t a
R e g u l a t i o n o f P r o t e i n a s e A c t i v i t y by H i g h M o l e c u l a r W e i g h t I n h i b i t o r s : B i o s y n t h e s i s o f R a t A l p h a -Ma c r o g l o t r u 1 i n s 183
T. G e i g e r , T. A n d u s , D. K u n z , M. H e i s i g , J . B a u e r , N. N o r t h o f f , F. G a u t h i e r , T.-A. T r a n - T h i , K. D e c k e r , and P. C. H e i n r i c h
I n d u c t i o n o f t h e P r o t e i n a s e I n h i b i t o r A l p h a - 2 -M a c r o g l o b u l i n i n R a t H e p a t o c y t e s by a M o n o c y t e - D e r i v e d F a c t o r 191
T. A n d u s , H. N o r t h o f f , J . B a u e r , U. G a n t e r , D. M ä n n e l , T.-A. T r a n - T h i , K. D e c k e r , and P. C. H e i n r i c h
A s t r o c y t e s S y n t h e s i z e and S e c r e t e A l p h a - 2 - M a c r o -g l o b u l i n : D i f f e r e n c e s B e t w e e n t h e R e g u l a t i o n o f A l p h a - 2 - M a c r o ] l . . j u l i n S y n t h e s i s i n R a t L i v e r and B r a i n 199
J . B a u e r , P . - J . G e o i c k e - H a e r t e r , U. G a n t e r , I . R i c h t e r , and W. G e r o k
C h a r a c t e r i z a t i o n o f D i f f e r e n t Forms o f D i p e p t i d y l P e p t i d a s e IV f r o m R a t L i v e r and Hepatoma by M o n o c l o n a l A n t i b o d i e s 207
S. H ä r t e l , C. H a n s k i , R. N e u m e i e r , R. G o s s r a u , and W. R e u t t e r
IV MUSCLE PROTEIN DEGRADATION
N o n - L y s o s o m a l , H i g h - M o l e c u l a r - M a s s C y s t e i n e P r o t e i n a s e s f r o m R a t S k e l e t a l M u s c l e 215
B. D a h l m a n n , L. K u e h n , F. Kopp, H. R e i n a u e r , and W. T. S t a u b e r
R o l e o f F a c t o r s D e r i v e d f r o m A c t i v a t e d M a c r o p h a g e s i n R e g u l a t i o n o f M u s c l e P r o t e i n T u r n o v e r 225
V . E . B a r a c o s
R e s p o n s e s o f L y s o s o m a l and N o n - L y s o s o m a l P r o t e a s e s t o U n l o a d i n g o f t h e S o l e u s 235
E. J . H e n r i k s e n , S. S a t a r u g , M. E. T i s c h l e r , and P. Fürst
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C a t h e p s i n B and D A c t i v i t y i n Human S k e l e t a l M u s c l e i n D i s e a s e S t a t e s 243
G. G u a r n i e r i , G. T o i g o , R. S i t u l i n , M. A. D e l B i a n c o , and L. C r a p e s i
H o r m o n a l R e g u l a t i o n o f M u s c l e P r o t e i n C a t a b o l i s m i n A c u t e l y U r e m i c R a t s : E f f e c t o f A d r e n a l e c t o m y and P a r a t h y r o i d e c t o m y 257
R. M. S c h a e f e r , M. M o s e r , P. K u l z e r , G. P e t e r , A. H e i d l a n d , W. H. H ö r l , and S. G. M a s s r y
V PROTEASES, KIDNEY AND UREMIA
R e l a t i o n B e t w e e n U r i n a r y P r o t e i n a s e s and P r o t e i n u r i e i n R a t s w i t h a G l o m e r u l a r D i s e a s e 267
J.-C. D a v i n , M. D a v i e s , J.-M. F o i d a r t , J . B. F o i d a r t , C. A. D e c h e n n e , and P. R. M a h i e u
C h a r a c t e r i z a t i o n and C l i n i c a l R o l e o f G l o m e r u l a r and Tubulär P r o t e a s e s f r o m Human K i d n e y 275
J . E. S c h e r b e r i c h , G. W o l f , C. S t u c k h a r d t , P. K u g l e r , and W. S c h o e p p e
E f f e c t o f G l o m e r u l a r P r o t e i n u r i e on t h e A c t i v i t i e s o f L y s o s o m a l P r o t e a s e s i n I s o l a t e d S e g m e n t s o f R a t P r o x i m a l T u b u l e 283
C. J . U l b r i c h t
M e p r i n P h e n o t y p e and C i c l o s p o r i n A T o x i c i t y i n M i c e 293
J . F. R e c k e l h o f f , S. S. C r a i g , R. J . B e y n o n , and J . S. Bond
P o t e n t i a l R o l e o f L y s o s o m a l P r o t e a s e s i n G e n t a m i c i n N e p h r o t o x i c i t y 305
C. J . O l b r i c h t , E. G u t j a h r , M. F i n k , and K. M. Koch
U r i n a r y P r o t e i n a s e A c t i v i t y i n P a t i e n t s w i t h A c u t e R e n a l F a i l u r e a f t e r Trauma and K i d n e y T r a n s p l a n t a t i o n 309
C. Wanner, S. G r e i b e r , G. K i r s t e , P. S c h o l l m e y e r , and W. H. Hörl
M e c h a n i s m s f o r A c t i v a t i o n o f P r o t e o l y s i s i n U r e m i a 315
W. E. M i t c h
E v i d e n c e f o r t h e R o l e o f P r o t e i n a s e s i n U r e m i c C a t a b o l i s m 323
R. M. S c h a e f e r , M. T e s c h n e r , G. P e t e r , J . L e i b o l d , P. K u l z e r , and A. H e i d l a n d
E g l i n C F a i l s t o Reduce C a t a b o l i s m i n A c t u e l y U r e m i c R a t s 331
M. T e s c h n e r , R. M. S c h a e f e r , C. R u d o l f , P. K u l z e r , G. P e t e r , and A. H e i d l a n d
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E v i d e n c e f o r P r o t e i n S p l i t P r o d u c t s i n P l a s m a o f P a t i e n t s w i t h A c u t e R e n a l F a i l u r e 339
M. Haag, H. E. M e y e r , P. S c h o l l m e y e r , and W. H. Hörl
P r o t e a s e s and A n t i p r o t e a s e s a t D i f f e r e n t V a s c u l a r S i t e s i n R e n a l F a i l u r e 345
K. B a u s e w e i n , K. S c h a f f e r h a n s , R. G ö t z , U. G i l g e , E. H e i d b r e d e r , and A. H e i d l a n d
P r o t e a s e H i s t o c h e m i s t r y i n N o r m a l and U r e m i c R a t s 351
R. G o s s r a u , A. H e i d l a n d , and J . H a u n s c h i l d
T o t a l K i n i n o g e n L e v e l s , P l a s m a R e n i n A c t i v i t y , D o p a m i n e - B e t a - H y d r o x y l a s e and P l a s m a C a t e c h o l a m i n e s i n C h r o n i c and A c u t e R e n a l F a i l u r e 361
K. M a r c z e w s k i , A. K s i a z e k , J . S o l s k i , and Z. P a c h u c k i
VI PROTEOLYTIC ENZYMES DÜRING EXTRACORPORAL CIRCULATION
B i o c o m p a t i b i l i t y o f D i a l y s i s Membranes: F a c t o r H B i n d i n g C o r r e l a t e s I n v e r s e l y w i t h Complement A c t i v a t i o n I n d i c ^ t . i g a L o c a l I m b a l a n c e o f I n v o l v e d P r o t e a s e s / A n t i - P r o t e a s e s 365
E. W. R a u t e r b e r g and E. R i t z
H e m o d i a l y s i s w i t h C u r o p h a n e Membranes L e a d s t o A l t e r a t i o n o f G r a n u l o c y t e O x i d a t i v e M e t a b o l i s m and L e u k o c y t e S e q u e s t i o n i n t h e Lung 377
G. K o l b , H. S c h ö n e m a n n , W. F i s c h e r , K. B i t t n e r , H. L a n g e , H. H ö f f k e n , V. Damann, K. J o s e p h , and K . Havemann
E f f e c t o f I m m u n s u p p r e s s i o n on t h e R e l e a s e o f M a i n G r a n u l o c y t e C o m p o n e n t s : I n V i v o and i n V i t r o S t u d i e s 385
C. Wanner, B. S i m o n , A. G ö s e l e , W. R i e g e l , P. S c h o l l m e y e r , and W. H. Hörl
R e l e a s e o f G r a n u l o c y t e P r o t e i n s Düring C a r d i o p u l m o n a r y B y p a s s : E f f e c t o f D i f f e r e n t P h a r m a c o l o g i c a l I n t e r v e n t i o n s 391
W. R i e g e l , G. S p i l l n e r , V. S c h l o s s e r , K. L a n g , and W. H. Hörl
S i g n i f i c a n t R o l e o f P r o t e a s e I n h i b i t i o n by A p r o t i n i n i n M y o c a r d i a l P r o t e c t i o n f r o m P r o l o n g e d C a r d i o p l e g i a w i t h H y p o t h e r m i a 399
M. S u n a m o r i , R. I n n a m i , H. F u j i w a r a , M. Yokoyama, A. S u z u k i
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F i b r i n o l y s i s C a u s e d by C a r d i o - P u l m o n a r y B y p a s s and Shed M e d i a s t i n a l B l o o d R e t r a n s f u s i o n -I s i t o f C l i n i c a l R e l e v a n c e ? 405
W. D i e t r i c h , A. B a r a n k a y , P. Wendt, A. S t e m b e r g e r , G. B l ü m e l , M. S p a n n a g l , M. Jochum, and J . A. R i c h t e r
V I I PROTEINASES IN CATABOLIC STATES
N u t r i t i o n and P r o t e a s e A c t i v i t y 411 J . D. K o p p l e
I n s u l i n D e g r a d a t i o n a f t e r I n j u r y i n Man 421 S. M. H o a r e , K. N. F r a y n , and R. E. O f f o r d
E n d o t o x i n A b o l i s h e s t h e I n d u c t i o n o f A l p h a - 2 - M a c r o -g l o b u l i n S y n t h e s i s i n C u l t u r e d Human M o n o c y t e s I n d i c a t i n g I n h i b i t i o n o f t h e T e r m i n a l M o n o c y t e M a t u r a t i o n i n t o M a c r o p h a g e s 425
J . B a u e r , U. G a n t e r , and W. G e r o k
L o c a l and G e n e r a l D e f e n c e M e c h a n i s m s i n B a c t e r i a l and C h e m i c a l P e r i t o n i t i s 433
A. L a s s o n , M. D e l s h a m m e r , and K. O h l s s o n
D e f i c i e n t P h a g o c y t o s i s S e c o n d a r y t o P r o t e o l y t i c B r e a k d o w n o f O p s o n i n s i n P e r i t o n i t i s E x u d a t e 441
A. B i l l i n g , ü. F r ö h l i c h , M. Jochum, and H. K o r t m a n n
P r o t e o l y s i s and L i p i d P e r o x i d a t i o n - Two A s p e c t s o f C e l l I n j u r y i n E x p e r i m e n t a l H y p o v o l e m i c -T r a u m a t i c S h o c k 449
H. R e d l , S. H a l l s t r ö m , C. L i e n e r s , W. F ü r s t , and G. S c h l a g
P l a s m a L e v e l s o f E l a s t a s e 1 P r o t e a s e I n h i b i t o r C o mplex i n t h e M o n i t o r i n g o f ARDS and M u l t i O r gan F a i l u r e - A Summary o f T h r e e C l i n i c a l T r i a l s 457
H. R e d l , E. P a u l , R. J . A. G o r i s , R. P a c h e r , W. W o l o s z c z u k , and G. S c h l a g
PMN E l a s t a s e and L e u k o c y t e N e u t r a l P r o t e i n a s e I n h i b i t o r ( L N P I ) f r o m G r a n u l o c y t e s as I n f l a m m a t i o n M a r k e r s i n E x p e r i m e n t a 1 -S e p t i c e m i a 465
R. G e i g e r , S. S o k a l , G. T r e f z , M. S i e b e c k , and H. H o f f m a n n
P l a s m a D e r i v a t i v e R e p l a c e m e n t T h e r a p y i n D i s s . I n t r a v a s c . C o a g . (DIC) I n d u c e d by S e p t i c D i s o r d e r s w i t h h i g h l y E l e v a t e d E l a s t a s e A l p h a - l - A T - C o m p l e x e s 473
R. E g b r i n g , R. S e i t z , M. W o l f , K. Havemann, L. L e r e n , H. B l a n k e , and G. F u c h s
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N e u t r o p h i l E l a s t a s e , T h r o m b i n and P l a s m i n i n S e p t i c S hock 481
R. S e i t z , M. W o l f , R. E g b r i n g , and K. Havemann
E l a s t a s e - A l p h a - l - P r o t e i n a s e I n h i b i t o r : An E a r l y I n d i c a t o r o f S e p t i c e m i a and B a c t e r i a l M e n i n g i t i s i n C h i l d h o o d 485
C. P. S p e e r , M. R e t h w i l m , and M. Gahr
Serum P a n c r e a t i c S e c r e t o r y T r y p s i n I n h i b i t o r ( P S T I ) i n S e r i o u s l y I n j u r e d and S e p t i c P a t i e n t s 493
H. T a n a k a , M. Ogawa, T. Y o s h i o k a , and T. S u g i m o t o
Changes i n P M N - E l a s t a s e i n B l o o d and i n R e n a l and P l a s m a K a l l i k r e i n - K i n i n S y s t e m s a f t e r S e v e r e B u r n I n j u r y 499
G. B o n n e r , W. N i e r m a n n , R. F e s t g e , and U. B ü c h s l e r
Serum P a n c r e a t i c S e c r e t o r y T r y p s i n I n h i b i t o r ( P S T I ) i n P a t i e n t s w i t h I n f l a m m a t o r y D i s e a s e s 505
M. Ogawa, T. S h i b a t a , T. N i i n o b u , K. Uda, N. T a k a t a , and T. M o r i
The E f f e c t o f A p r o t i n i n A d m i n i s t r a t i o n on t h e I n t r a o p e r a t i v e H i s t a m i n e R e l e a s e and H a e m o s t a t i c D i s o r d e r s 509
H. H a r k e and S. Rahman
I n c r e a s e d M o r t a l i t y i n S e p t i c R a t s a f t e r L e u p e p t i n A p p l i c a t i o n 515
E. K o v a t s , J . K a r n e r , G. O l l e n s c h l ä g e r , J . K a r n e r , A. S i m m e l , and E. R o t h
L y s o s o m a l Enzymes and G r a n u l o c y t e E l a s t a s e i n S y n o v i a l F l u i d a f t e r M u l t i p l e T r a u m a t i c I n j u r i e s 519
M. Hörl and H. P. B r u c h
A S e r i n e P r o t e i n a s e I n h i b i t o r i n Human A r t i c u l a r C a r t i l a g e - P o s s i b l e R o l e i n t h e P a t h o g e n e s i s o f I n f l a m m a t o r y J o i n t D i s e a s e s 523
H. B u r k h a r d t , M. K a s t e n , and S. R a u l s
D e t e c t i o n o f G r a n u l o c y t e E l a s t a s e S p e c i f i c IgG S p l i t P r o d u c t s i n R h e u m a t o i d S y n o v i a l F l u i d 531
I . E c k l e , G. K o l b , F. N e u r a t h , and K. Havemann
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V I I I PROTEASES AND MALIGNOMA
The T C e l l S p e c i f i c S e r i n e P r o t e i n a s e T S P - 1 : B i o c h e m i c a l C h a r a c t e r i z a t i o n , G e n e t i c A n a l y s i s , and F u n c t i o n a l R o l e 535
H.-G. S i m o n , U. F r u t h , R. G e i g e r , M. D. K r a m e r , and M. M. Simon
P a n c r e a t i c S e c r e t o r y T r y p s i n I n h i b i t o r i n C a n c e r 547
M. Ogawa, N. T o m i t a , A. H o r i i , N. M a t s u u r a , M. H i g a s h i y a m a , T. Yamamoto, A. M u r a t a , T. M o r i , and K. M a t s u b a r a
P r o t e a s e s and A n t i p r o t e a s e s i n A s c i t e s -D i f f e r e n t i a t i o n o f M a l i g n a n t and Non-m a l i g n a n t A s c i t e s and P r e d i c t i o n o f C o a g u l o p a t h y i n A s c i t e s R e t r a n s f u s i o n 555
J . S c h ö l m e r i c h , E. K ö t t g e n , B. A. V o l k , and W. G e r o k
A l p h a - l - A n t i t r y p s i n and A l p h a - l - A n t i c h y m o t r y p s i n Serum L e v e l i n R e l a t i o n t o S t a g i n g and P o s t o p e r a t i v e C l i n i c a l C o u r s e o f Human C o l o r e c t a l C a n c e r 561
A. K u r y l i s z y n - M o s k a l , K. B e r n a c k a , and S. S i e r a k o w s k i
I n h i b i t i o n o f P r o t e a s e s Düring E x t r a c o r p o r e a l E x t r e m i t y P e r f u s i o n 565
H. W a l t h e r , H. Mü l l e r , and K. R. A i g n e r
INDEX 569
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D E F I C I E N T PHAGOCYTOSIS SECONDARY TO PROTEOLYTIC BREAKDOWN OF
OPSONINS IN P E R I T O N I T I S EXUDATE
A. B i l l i n g 3 , D. F r ö h l i c h 9 , M. J o c h u m b and H. K o r t m a n n a
a) C h i r u r g i s c h e K l i n i k und P o l i k l i n i k d e r U n i v e r s i tät M ü n c h e n , K l i n i k u m G r o ß h a d e r n , M a r c h i o n i n i -s t r . 15, 8000 München 70, Germany
b) I n s t i t u t für k l i n i s c h e Chemie und k l i n i s c h e B i o c h e m i e d e r U n i v e r s i t ä t M ü n c h e n
INTRODUCTION
In P e r i t o n i t i s , p r o p e r f u n c t i o n i n g o f t h e i n t r a a b d o m i n a l l o c a l d e f e n c e S y s t e m i s c r u c i a l f o r a f a v o u r a b l e o u t c o m e and s u r v i v a l o f t h e p a t i e n t . P e r i t o n i t i s e x u d a t e i s c h a r a c t e r i z e d by t h e p r e s e n c e o f a l a r g e number o f v i a b l e b a c t e r i a d e s p i t e a huge p o p u l a t i o n o f i n t a c t P M N - 1 e u k o c y t e s . A l t h o u g h p h a g o c y t e f u n c t i o n , t h e main f a c t o r o f c e l l u l a r d e f e n c e , i s i n t a c t o r e v e n s t i m u l a t e d i n P e r i t o n i t i s e x u d a t e ( 1 , 2 ) , t h e r e i s no a d e q u a t e e x p l a n a t i o n o f how b a c t e r i a c a n p e r s i s t i n s u r r o u n d i n g s r i e h i n P M N - 1 e u k o c y t e s .
An a d e q u a t e s u f f i c i e n t i n t r a a b d o m i n a l h o s t d e f e n c e r e s u l t s f r o m a b a l a n c e d C o o p e r a t i o n b e t w e e n c e l l u l a r and f l u i d p h a s e c o m p o n e n t s . The h u m o r a l immune p r o c e s s o f r e c o g n i z i n g and l a b e l l i n g a m i c r o b e as a n t i g e n i c a 1 1 y f o r e i g n i s d e s c r i b e d as o p s o n i z a t i o n . T h i s c a n p r o e e e d v i a n o n - s p e e i f i e o r s p e c i f i c m e c h a n i s m s ( 3 ) . The l a t t e r i s I m m u n o g l o b u l i n G ( I g G ) d e p e n d e n t . ßoth p a t h w a y s r e s u l t i n c o m p l e m e n t a c t i v a t i o n w h i c h l e a d s t o a l i b e r a t i o n o f O p s o n i n s , m e d i a t o r s o f i n f l a m m a t i o n and m i c r o -b i c i d a l c o m p o n e n t s . The main f a c t o r s o f o p s o n i z a t i o n a r e C3-d e r i v e d c o m p l e m e n t c o m p o n e n t s and IgG. P h y s i o l o g i c a l C3 a c t i v a t i o n r e s u l t s i n i t s b r e a k d o w n i n t o t h e f r a g m e n t s C3c and C3d. U n s p e c i f i c p r o t e o l y t i c b r e a k d o w n o f o p s o n i c f a c t o r s i n p l e u r a l empyema has a l s o been d e s c r i b e d ( 4 ) .
P h a g o c y t o s i s l e a d s t o c e l l a c t i v a t i o n and a l s o r e s u l t s i n an e x t r a c e l l u l a r r e l e a s e o f l y s o s o m a l and o x i d a t i v e g r a n u l o c y t e enzymes ( 5 ) . M y e l o p e r o x i d a s e i s known t o i m p a i r o p s o n i z a t i o n ( 6 ) . P r o t e o l y t i c and o x i d a t i v e d e s t r u e t i o n c a n d e s t r o y b i o l o g i -c a l a c t i v i t y o f p r o t e i n c o m p o n e n t s w i t h o u t a l t e r i n g t h e i r a n t i -g e n i c i t y . T h u s , d e s p i t e immunol o g i c a 1 l y d e t e r m i n e d h i g h c o n c e n -t r a t i o n s , t h e r e may be a f u n c t i o n a l d e f i c i t i n s u c h f a c t o r s . In p a r a l l e l t o enzyme r e l e a s e , p a r t i c l e a t t a c h m e n t l e a d s t o a s t r o n g a c t i v a t i o n o f o x y g e n m e t a b o l i s m i n p h a g o c y t e s , r e s u l t i n g i n t h e g e n e r a t i o n o f o x y g e n - d e r i v e d f r e e r a d i c a l s . T h e s e m i c r o -
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b i c i d a l and c y t o t o x i c s u b s t a n c e s a r e known t o d e s t r o y ^ . - P r o t e i n a s e i n h i b i t o r ( o ^ P I ) . U s i n g a P h o t o m e t r i e ampl i f i c a t i o n S y s t e m , t h e r e l e a s e öf o x y g e n - d e r i v e d f r e e r a d i c a l s c a n be m e a s u r e d as c h e m i 1 u m i n e s c e n c e ( C L ) and i s assumed t o be a q u a n t i t a t i v e p a r a m e t e r f o r p h a g o c y t i c a c t i v i t y . U s i n g a c o n s t a n t number o f p h a g o c y t e s , C L - m e a s u r e m e n t s can be u s e d as a d i r e c t P a r a m e t e r f o r t h e q u a l i t y o f p a r t i c l e o p s o n i z a t i o n ( 7 , 8 ) .
L i t t l e i s known a b o u t i n t r a a b d o m i n a l o p s o n i z a t i o n . We d e v e l o p e d a s i m p l e CL a s s a y t o e v a l u a t e o p s o n i c a c t i v i t y (OA) i n P e r i t o n i t i s e x u d a t e s and s e r u m s a m p l e s o f p a t i e n t s w i t h a c u t e and p e r s i s t i n g P e r i t o n i t i s . The l a t t e r g r o u p was t r e a t e d w i t h E t a p p e n l a v a g e w h i c h means p l a n n e d r e l a p a r o t o m y u n t i l c l e a r a n c e o f t h e a b d o m i n a l c a v i t y . In a d d i t i o n , we i n v e s t i g a t e d O p s o n i n l e v e l s as w e l l as r e l e a s e d g r a n u l o c y t i c p r o t e i n s .
MATERIAL AND METHODS
P a t i e n t s
50 a b d o m i n a l e x u d a t e s and c o r r e s p o n d i n g b l o o d s a m p l e s were drawn i n t r a o p e r a t i v e 1 y f r o m 27 p a t i e n t s w i t h d i f f u s e p u r u l e n t P e r i t o n i t i s . E x u d a t e s were c e n t r i f u g a t e d , w h i l e b l o o d was p r o c e s s e d i n t o serum and E D T A - p l a s m a .
C h e m i 1 u m i n e s c e n c e a s s a y f o r o p s o n i c a c t i v i t y
Zymosan was p r e o p s o n i z e d w i t h p o o l e d n o r m a l s e r u m , p a t i e n t s ' s e r u m o r p a t i e n t s ' e x u d a t e . The f i n a l c h e m i 1 u m i n e s c e n c e a s s a y c o n t a i n e d 0,05 ml d i l u t e d E D T A - b l o o d ( 1 / 1 5 ) f r o m h e a l t h y v o l u n t e e r s , 0,8 ml V e r o n a l b u f f e r and 0,1 ml L u m i n o l S o l u t i o n ( 9 ) . The r e a c t i o n was s t a r t e d by a d d i n g 0,05 ml o f t h e o p s o n i z e d zymosan ( 2 0 mg/ml). The 30 m i n . i n t e g r a l o f c h e m i 1 u m i n e s c e n c e was c a l c u l a t e d . In e a c h a s s a y zymosan o p s o n i z e d w i t h n o r m a l s e r u m , p a t i e n t s ' s erum and p a t i e n t s ' e x u d a t e was t e s t e d s i m u l t a n e o u s l y . As a l l o t h e r c o n d i t i o n s ( b l o o d and b u f f e r c o n c e n t r a t i o n ) were i d e n t i c a l , t h e r e s u l t i n g d i f f e r e n t c h e m i 1 u m i n e s c e n c e r e s p o n s e i s due t o t h e q u a l i t y o f o p s o n i z a t i o n ( 1 0 ) . O p s o n i c a c t i v i t y was e x p r e s s e d as a p e r c e n t a g e o f t h e n o r m a l s e r u m v a l u e .
O p s o n i n s t u d i e s
C3 and IgG l e v e l s were m e a s u r e d w i t h a S t a n d a r d r a d i a l i m m u n o d i f f u s i o n a s s a y ( B e h r i n g w e r k e M a r b u r g , n o r m a l v a l u e s : IgG 1250 mg/dl and C3 82 m g / d l ) . C3 S p l i t t i n g was d e m o n s t r a t e d by c r o s s e d i m m u n o e l e c t r o p h o r e s i s a e c o r d i n g t o G a n r o t h ( 1 1 ) e m p l o y i n g a C3c a n t i b o d y ( B e h r i n g w e r k e M a r b u r g ) .
T e s t s f o r PMN-enzymes
E l a s t a s e i n c o m p l e x w i t h o c . - p r o t e i n a s e i n h i b i t o r ( o C P I ) and m y e l o p e r o x i d a s e c o n c e n t r a t i ö n s were m e a s u r e d by E L I S A : p l a s m a r e f e r e n c e f o r c o m p l e x e d e l a s t a s e : 50-181 u g / 1 , and f o r m y e l o p e r o x i d a s e : 25-47 ug/1 ( 1 2 , 1 3 ) . F r e e e l a s t a s e a c t i v i t y was m e a s u r e d w i t h a c h r o m o g e n i c S u b s t r a t e ( 1 4 ) o r by a d d i n g o ^ P I and t h e n r e - a s s a y i n g e l a s t a s e - o c PI c o m p l e x .
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RESULTS
O p s o n i z a t i o n i n s e r u m
In a c u t e P e r i t o n i t i s C3 and IgG s e r u m l e v e l s were c l o s e t o t h e l o w e r l i m i t o f t h e n o r m a l ränge and were i n c r e a s e d i n p a t i e n t s w i t h p e r s i s t i n g P e r i t o n i t i s ( T a b l e 1 ) . O p s o n i c a c t i v i t y i n p a t i e n t s ' s erum was w e l l c o r r e l a t e d w i t h a C3/IgG i n d e x w h i c h r e s u l t s f r o m a d d i t i o n o f C3 and IgG c o n c e n t r a t i o n s . C o m p u t e r i z e d c o r r e l a t i o n a n a l y s i s r e s u l t e d i n a S - s h a p e d c u r v e . v e r y s i m i l a r t o a d i l u t i o n c u r v e o f n o r m a l serum ( F i g . 1 ) . In F i g . 1 s e r u m s a m p l e s o f p a t i e n t s (n=23) w i t h a c u t e and p e r s i s t i n g P e r i t o n i t i s a t t h e t i m e o f s a m p l e c o l l e c t i o n were i n -c 1 u d e d .
T a b l e
IgG
C3
OA
O p s o n i n l e v e l s ( I g G , C3) and o p s o n i c a c t i v i t y (OA) i n p a t i e n t serum (% o f n o r m a l - S t a n d a r d d e v i a t i o n )
a c u t e P e r i t o n i t i s (n=13)
62.8 i 29.3
65.3 t 23.1
85.8 - 33.5
p e r s i s t i n g p e r i t o n i t i s l (n=14)
109.1 - 30.8
83.0 i 21.6
115.4 - 20.8
> o < o O C/) CL o
2 0 0
1 6 0 -
1 2 0
C 3 - l g C - I N D E X (%)
F i g . 1. C o r r e l a t i o n o f o p s o n i c a c t i v i t y and O p s o n i n c o n c e n t r a -t i o n i n p a t i e n t s e r u m . The C 3 - I g G - i n d e x r e s u l t s f r o m a d d i t i o n o f serum c o n c e n t r a t i o n s o f b o t h p a r a m e t e r s . The c u r v e d e m o n s t r a t e s t h e c o r r e l a t i o n f r o m s e r i a l d i l u t i o n s o f n o r m a l s e r u m ( 1 : 2 t o 1 : 1 0 ) .
O p s o n i z a t i o n i n e x u d a t e
In P e r i t o n i t i s e x u d a t e s , mean p r o t e i n c o n t e n t was 66 % o f
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s e r u m l e v e l s i n a c u t e P e r i t o n i t i s and 62 % o f s e r u m l e v e l s i n E t a p p e n 1 a v a g e . The e l e c t r o p h o r e t i c p r o t e i n d i s t r i b u t i o n p a t t e r n was s i m i l a r t o s e r u m , i n d i c a t i n g p e r i t o n e a l p e r m e a b i l i t y e v e n f o r l a r g e m o l e c u l e s . O p s o n i n c o n c e n t r a t i o n s a r e l i s t e d i n T a b l e 2. A c c o r d i n g t o t h e s e r u m c o r r e l a t i o n o f O p s o n i n c o n c e n -t r a t i o n and f u n c t i o n , t h e s e O p s o n i n l e v e l s s h o u l d r e s u l t i n an o p s o n i c a c t i v i t y o f 58 % o f n o r m a l i n a c u t e P e r i t o n i t i s and 56 % o f n o r m a l i n E t a p p e n 1 a v a g e . The e x p e r i m e n t a l d e t e r m i n a t i o n o f o p s o n i c f u n c t i o n , h o w e v e r , showed a much l o w e r a c t i v i t y ( 8 . 4 % and 4.6 % o f n o r m a l , r e s p e c t i v e l y ) i n d i c a t i n g a p r o -n o u n c e d d e f i c i t i n p a r t i c l e o p s o n i z a t i o n i n P e r i t o n i t i s e x u d a t e s .
T a b l e 2. O p s o n i n l e v e l s ( I g G , C3) and o p s o n i c a c t i v i t y (OA) i n P e r i t o n i t i s e x u d a t e s (% o f n o r m a l s e r u m v a l u e - S t a n d a r d d e v i a t i o n ) . OA i s t h e e x p e c t e d OA a c c o r d i n g t o t h e c o r r e l a t i o n ö e t ween IgG/C3 and OA i n s e r u m , 0 A r e a l i s t h e a c t u a ^ ^ A i n e x u d a t e .
a c u t e P e r i t o n i t i s E t a p p e n 1 a v a g e (n=13) (n=14)
IgG 43.9 - 21.3 52.9 - 18.1
C3 35.8 - 27.8 25.5 ± 6.8
OA
OA
exp
r e a l
58
8.4
56
4.6
To e v a l u a t e O p s o n i n b r e a k d o w n , c r o s s e d i m m u n o e l e c t r o p h o -r e s i s was c a r r i e d o u t i n 6 p a t i e n t s ' s e r u m and e x u d a t e s a m p l e s
a C3c a n t i b o d y . In P e r i t o n i t i s s e r u m o n l y a s m a l l C3 was f r a g m e n t e d ( F i g . 2 b ) . In e x u d a t e , h o w e v e r , on t h e l e u k o c y t e c o n c e n t r a t i o n , a g r e a t p a r t ( F i g . 3 c) a l l ( F i g . 3d) C3 was s p l i t i n t o f r a g m e n t s o f l o w e r w e i g h t . T h u s , t h e o p s o n i c d e f i c i t i n p u r u l e n t e x u d a t e s
by an e x t e n s i v e b r e a k d o w n o f t h e c o m p l e m e n t
e m p l o y i ng amount o f d e p e n d i ng o r a l m o s t m o i e c u l a r was a c c o m p a n i e d f a c t o r C3.
"A C)
d)
F i g
b)
c )
d)
no C3 o n l y
s p l i t t i n g t r a c e amounts o f C3 b r e a k d o w n
C r o s s e d i m m u n o e l e c t r o p h o r e s i s f o r C3 i n serum and e x u d a t e . a) N o r m a l s e r u m ,
P a t i e n t s e r u m ;
p r o d u c t s E x u d a t e ( 2 2 , 0 0 0 l e u k o c y t e s / m m 3 ) , p r o n o u n c e d C3 S p l i t t i n g i n t o s m a l l e r c o m p o n e n t s ( r i g h t p e a k ) P u r u l e n t P e r i t o n i t i s e x u d a t e ( 1 1 0 , 0 0 0 ) l e u k o c y t e s / mm 3), a l m o s t c o m p l e t e b r e a k d o w n o f C3
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U n s p e c i f i c p r o t e o l y t i c and o x i d a t i v e a c t i v i t y i n P e r i t o n i t i s e x u d a t e
In 27 e x u d a t e s , we q u a n t i f i e d c o m p l e x e d P M N - e l a s t a s e and m y e l o p e r o x i d a s e l e v e l s . E l a s t a s e c o n c e n t r a t i o n s were e l e v a t e d up t o 250 mg/1, w h i c h i s 2000 t i m e s h i g h e r t h a n t h e n o r m a l p l a s m a r ä n g e . We a l s o f o u n d e x t r e m e l y h i g h c o n c e n t r a t i o n s f o r m y e l o p e r o x i d a s e , r e a c h i n g up t o 160 mg/1 ( T a b l e 3 ) .
T a b l e 3. C o m p l e x e d P M N - e l a s t a s e and m y e l o p e r o x i d a s e l e v e l s i n P e r i t o n i t i s e x u d a t e s (mean - S t a n d a r d d e v i a t i o n , M 9 / D .
a c u t e P e r i t o n i t i s E t a p p e n 1 a v a g e (n=13) (n=14)
e l a s t a s e (-cc P I ) 75,972 ± 52,366 8 9 , 8 5 3 - 67,570
m y e l o p e r o x i d a s e 34,458 ± 42,661 55,402 ± 39,005
In s e v e r a l e x u d a t e s we c o u l d d e m o n s t r a t e f r e e e l a s t a s e a c t i v i t y , b o t h w i t h a s p e c i f i c c h r o m o g e n i c S u b s t r a t e and an
od. P l - b i n d i n g a s s a y . In some e x u d a t e s up t o 70 % o f t h e t o t a l e l a s t a s e c o n t e n t was f o u n d t o be u n i n h i b i t e d f r e e e l a s t a s e . The c o n c e n t r a t i o n f o r - p r o t e i n a s e i n h i b i t o r i n t h e s e e x u d a t e s r a n g e d f r o m 99 t o 341 m ^ / d l , w h i c h , c a l c u l a t e d on t h e b a s i s o f t h e m o l a r r a t i o o f i n h i b i t o r c o n c e n t r a t i o n v e r s u s P r o t e i n a s e , s h o u l d be s u f f i c i e n t f o r c o m p l e t e e l a s t a s e i n h i b i t i o n . In p a t i e n t s w i t h g a s t r o i n t e s t i n a l P e r f o r a t i o n , i n t r a a b d o m i n a l e l a s t a s e l e v e l s v a r i e d w i t h i n a w i d e ränge ( T a b l e 4 ) .
T a b l e 4. E l a s t a s e ( i n c o m p l e x o r a c t i v e ) and o ^ . - P r o t e i n a s e i n h i b i t o r (<x\PI) i n P e r i t o n i t i s e x u d a i e s .
cC P I - e l a s t a s e c ö m p l e x ( m g / 1 )
f r e e e l a s t a s e (mg/1)
t o t a l e l a s t a s e (mg/1)
t o t a l oC.PI (mg/1 1)
P a t . 1 120.6 272 .3 392.9 2250
P a t . 2 45.7 0.5 46.2 1610
P a t . 3 111.1 1 .6 112.7 1060
P a t . 4 54.6 73. 1 127.7 990
To i n v e s t i g a t e t h e p o s s i b l e i n f l u e n c e o f p r o t e o l y t i c l y s o s o m a l enzymes on o p s o n i c a c t i v i t y we c o m p a r e d b o t h p a r a m e t e r s . C o r r e l a t i o n o f t h e o p s o n i c d e f i c i t w i t h e l a s t a s e l e v e l s i n e x u d a t e s r e v e a l e d t h a t o n l y e x u d a t e s w i t h a low c o n c e n t r a t i o n o f c o m p l e x e d e l a s t a s e (<10 m g / / l ) r e a c h e d an a l m o s t n o r m a l o p s o n i c a c t i v i t y , w h e r e a s e x u d a t e s w i t h h i g h e l a s t a s e c o n c e n -t r a t i o n s were d e f i c i e n t i n o p s o n i c f u n c t i o n ( F i g . 3 ) .
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C 3 - l g G - I N D E X (%)
F i g . 3. C o r r e l a t i o n o f o p s o n i c a c t i v i t y and e l a s t a s e c o n c e n t r a t i o n i n P e r i t o n i t i s e x u d a t e s . The c u r v e d e m o n s t r a t e s t h e r e l a t i o n b e t w e e n O p s o n i n c o n c e n t r a t i o n and o p s o n i c a c t i v i t y i n n o r m a l s e r u m . O n l y e x u d a t e s w i t h e l a s t a s e c o n c e n t r a t i o n s <10 mg/1 r e v e a l a d e q u a t e o p s o n i c a c t i v i t y .
DISCUSSION
The C L - a p p r o a c h d e s c r i b e d h e r e , p r o v i d e s a r a p i d , r e -l i a b l e n o n - d e s t r u c t i v e method f o r q u a n t i t a t i v e a n a l y s i s o f o p s o n i c c a p a c i t y i n serum and e x u d a t e . T h e r e b y , i n n o r m a l as w e l l as i n p a t i e n t serum t h e key r o l e o f IgG and C3 f o r o p s o n i z a t i o n c o u l d be c o n f i r m e d .
L i t t l e I n f o r m a t i o n i s a v a i l a b l e a b o u t i n t r a p e r i t o n e a l f l u i d - p h a s e d e f e n c e a c t i v i t y . In p l e u r a l empyema, d e f i c i e n t p h a g o c y t o s i s due t o b r e a k d o w n o f O p s o n i n s has been d e s c r i b e d ( 4 ) . We c o u l d d e m o n s t r a t e a h i g h p e r i t o n e a l p e r m e a b i l i t y i n P e r i t o n i t i s g i v i n g way e v e n f o r l a r g e p r o t e i n s . D e s p i t e s u f f i c i e n t i m m u n o l o g i c a l l y m e a s u r a b l e O p s o n i n l e v e l s o u r r e s u l t s r e v e a l e d an e x t e n d e d d y s f u n c t i o n o f p a r t i c l e o p s o n i z a t i o n i n human P e r i t o n i t i s e x u d a t e s . Most o f t h e i m m u n o l o g i c a l l y f o u n d O p s o n i n s were f u n c t i o n a l l y d e s t r o y e d . The c r o s s e d immuno-e l e c t r o p h o r e s i s gave e v i d e n c e t h a t p u r u l e n t P e r i t o n i t i s e x u d a t e s c o n t a i n e d h a r d l y any i n t a c t p h y s i o l o g i c a l l y a c t i v e C3. The i d e n t i f i e d C3 f r a g m e n t s seem t o be d e g r a d e d p r o d u c t s w i t h o u t o p s o n i c f u n c t i o n .
In e x u d a t e s we f o u n d e x t r e m e l y h i g h l e v e l s o f P M N - e l a s t a s e ( m o s t o f i t i n c o m p l e x w i t h o t-PI) and m y e l o p e r o x i d a s e , i n d i c a t i n g t h e r e l e a s e o f a m a j o r p a r t o f t h e t o t a l p h a g o c y t i c enzyme c o n t e n t . Due t o a s l o w p e r i t o n e a l c l e a r a n c e o f e l a s t a s e -
oC.PI c o m p l e x e s , enzyme c o n c e n t r a t i o n s a r e f u r t h e r i n c r e a s e d . D e s p i t e an i m m u n o l o g i c a l l y s u f f i c i e n t c o n c e n t r a t i o n o f «i.PI we c o u l d d e m o n s t r a t e f r e e e l a s t a s e a c t i v i t y i n some e x u d a t e s a m p l e s . O x i d a t i v e i m p a i r m e n t o f o ^ P I has been d e s c r i b e d ( 1 5 )
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and may be due t o t h e r e l e a s e o f m y e l o p e r o x i d a s e and h i g h l y r e a c t i v e o x y g e n p r o d u c t s d u r i n g p h a g o c y t o s i s .
F o r t h e f i r s t t i m e t h e s e d a t a r e v e a l c l e a r l y t h a t t h e d y s f u n c t i o n o f t h e i n t r a a b d o m i n a l d e f e n c e s y s t e m i n a c u t e P e r i t o n i t i s r e s u l t s f r o m i m p a i r e d o p s o n i c c a p a c i t y . One m a j o r u n d e r l y i n g p a t h o m e c h a n i s m may be o x i d a t i v e i n a c t i v a t i o n o f t h e <x.-proteinase i n h i b i t o r t h u s a l l o w i n g u n s p e c i f i c p r o t e o l y t i c O p s o n i n d e g r a d a t i o n by f r e e l y s o s o m a l e n z y m e s . F o r f u r t h e r i m p r o v e m e n t i n t h e r a p y t h e e f f e c t o f l o c a l p r o t e i n a s e -i n h i b i t o r a p p l i c a t i o n has t o be c o n s i d e r e d .
Ac k n o w l e d g m e n t
We t h a n k D i p l . - I n g . B. S c h m i d t f r o m t h e n e p h r o l o g y r e s e a r c h l a b (Med. K l i n i k I d e r U n i v e r s i t ä t München) f o r t h e P e r f o r mance o f t h e c r o s s e d i m m u n o e 1 e c t r o p h o r e s i s .
REFERENCES
1 ) J . F r e i s c h l a g ^ . B a c k s t r o m , D . K e l l y , G. Keehn , B. a . R . B u s u t t i 1 C o m p a r i s o n o f b l o o d and p e r i t o n e a l n e u t r o p h i l a c t i v i t y i n r a b b i t s w i t h and w i t h o u t P e r i t o n i t i s J . o f S u r g . R e s . ; 40: 1 4 5 - 1 5 1 , 1935
2) A. B i l l i n g , H. K o r t m a n n N a c h w e i s z e l l u l ä r e r und h u m o r a l e r A b w e h r d e f e k t e b e i d e r e i t r i g e n P e r i t o n i t i s m i t e i n e m m o d i f i z i e r t e n C h e m i 1 u m i n e s -z e n z v e r f a h r e n A c t a c h i r . A u s t r i a c a e 3: 3 4 0 - 3 4 1 , 1986
3) H. Hahn M e c h a n i s m e n d e r k ö r p e r e i g e n e n I n f e k t a b w e h r FAC, Band 3-2, 139-150, 1984
4) F . A . W a l d v o g e l , P . V a u d a u x , P . D . L e w , A . Z w a h l e n , S . S u t e r , U . N y d e g g e r D e f i c i e n t p h a g o c y t o s i s s e c o n d a r y t o b r e a k d o w n o f o p s o n i c f a c t o r s i n i n f e c t e d e x u d a t e s A d v . E x p . M e d . a n d B i o l . 141: 6 0 3 - 6 1 0 , 1984
5) K. O h l s s o n , I . O l s s o n The e x t r a c e l l u l a r r e l e a s e o f g r a n u l o c y t e c o l l a g e n a s e and e l a s t a s e d u r i n g p h a g o c y t o s i s and i n f l a m m a t o r y p r o c e s s e s S c a n d . J . H a e m a t o l . JI9: 1 4 5 - 1 52, 1 977
6) B. I . C o b 1 e , C . D a h 1 g r e n , J . H e d , O . S t e n d h a l M y e l o p e r o x i d a s e r e d u c e s t h e o p s o n i z i n g a c t i v i t y o f Immung l o b u l i n G and c o m p l e m e n t c o m p o n e n t C3b B i o c h e m . e t B i o p h y s . A c t a 8 0 2 : 5 0 1 - 5 0 5 , 1987
7) P . B e i l a v i t e , P . D r i , V . D e i l a B i a n c a , M . C . S e r r a The m e a s u r e m e n t o f S u p e r o x i d e a n i o n p r o d u c t i o n by Immung l o b u l i n G and c o m p l e m e n t c o m p o n e n t C3b E u r o p . J.C1 i n . I n v e s t . J_3: 3 6 3 - 3 6 8 , 1 983
8) R . C . A l l e n , M . L i e b e r m a n K i n e t i c a n a l y s i s o f m i c r o b e o p s o n i f i c a t i o n b a s e d on s t i m u -l a t e d p o l y m o r p h n u c l e a r l e u k o c y t e o x y g e n a t i o n a c t i v i t y I n f . a n d Imm. 45: 4 7 5 - 4 8 2 , 1984
4 4 7
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9) D . I n t h o r n , T h . S z c z e p o n i k , B . M ü h l b a y e r , M . J o c h u m , H . R e d l S t u d i e s o f g r a n u l o c y t e f u n c t i o n ( c h e m i 1 u m i n e s c e n c e r e s p o n s e ) i n p o s t o p e r a t i v e i n f e c t i o n . I n : S c h l a g , G., R e d l , H. e d s . ; F i r s t v i e n n a s h o c k f o r u m , P a r t B. P r o q r . i n C l i n . a n d B i o l . R e s . 263B: 5 1 - 5 8 , 1987
10) R.C. A l l e n , M.M. L i e b e r m a n n K i n e t i c a n a l y s i s o f m i c r o b e o p s o n i f i c a t i o n b a s e d on s t i -m u l a t e d p o l y m o r p h o n u c l e a r l e u k o c y t e o x y g e n a t i o n a c t i v i t y I n f , and Imm. 45: 4 7 5 - 4 8 2 , 1984
11) PO G a n r o t h C r o s s e d i m m u n o e l e c t r o p h o r e s i s S c a n d . J.C1 i n . L a b . I n v e s t . 29: 3 9 - 4 1 , 1 972
12) S.Neumann, G . G u n z e r , N . H e n n r i c h , H.Lang P M N - e l a s t a s e a s s a y : enzyme i m m u n o a s s a y f o r human p o l y m o r p h o n u c l e a r e l a s t a s e c o m p l e x e d w i t h «c,-proteinase i n h i b i t o r J.C1 i n . C h e m . C l i n . B i o c h e m . _22: 6 9 3 - 6 9 7 , 1 984
13) S.Neumann, G . G u n z e r , H.Lang, M.Jochum, H . F r i t z Q u a n t i t a t i o n o f m y e l o p e r o x i d a s e f r o m human g r a n u l o c y t e s as an i n f l a m m a t i o n m a r k e r by e n z y m e - 1 i n k e d i m m u n o s o r b e n t a s s a y F r e s e n i u s Z . A n a l Chem. 324: 365, 1986
14) M. Jochum, A. B i t t n e r I n t e r - * - t r y p s i n i n h i b i t o r o f human s e r u m : an i n h i b i t o r o f p o l y m o r p h o n u c l e a r g r a n u l o c y t e e l a s t a s e Hoppe S e y l e r ' s Z . P h v s i o l . C h e m . 364: 1 7 0 9 - 1 7 1 5 , 1983
15) N . R . M a t h e s o n , P.S.Wong, J . T r a v i s E n z y m a t i c i n a c t i v a t i o n o f human PI by n e u t r o p h i l m y e l o -p e r o x i d a s e B i o c h e m . B i o p h v s . R e s . C o m m . 88: 402, 1979
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INDEX
A c i d P h o s p h a t a s e , 412
A c i d p r o t e a s e , 239
A c u t e p h a s e r e a c t a n t s , 171
A c u t e r e n a l f a i l u r e , 3 0 9 , 3 23,
339, 3 4 5 , 361
A c u t e u r e m i a , 331
A c y l a t i o n , 161
A d r e n a l e c t o m y , 257
A d u l t r e s p i r a t o r y d i s t r e s s
S y n d r o m e , 17, 149
A f f i n i t y c h r o m a t o g r a p h y , 36
AIDS, 3
A l a n y l a m i n o p e p t i d a s e , 351
A l k a l i n e p r o t e a s e , 239, 326,
334
A l p h a , -
a n t i c h y m o t r y p s i n , 97, 1 7 1 ,
561
a n t i t r y p s i n , 1 4 5 , 4 7 3 , 496,
505, 561
i n h i b i t o r , 191
m a c r o g l o b u l i n , 183
p r o t e a s e i n h i b i t o r , 346,
434, 555
P r o t e i n a s e , 405
P r o t e i n a s e i n h i b i t o r , 4 2 ,
97, 107, 120, 123,
171, 385, 393
A l p h a 2 -
a n t i p l a s m i n , 127, 434, 4 7 3 ,
515, 555
m a c r o g l o b u l i n , 127, 145,
171, 183, 1 9 1 , 199,
346, 4 2 5 , 434, 496,
500, 555
A l p h a - D - g a l a c t o s i d a s e , 46
A l p h a - D - g l u c o s i d a s e , 46
A l p h a - m a c r o g l o b u l i n s , 183
A I v e o l a r - a r t e r i a l o x y g e n
t e n s i o n d i f f e r e n c e , 151
A m i n o p e p t i d a s e A, 278
A m i n o p e p t i d a s e M, 279
A n g i o t e n s i n C o n v e r t i n g enzyme,
13, 145
A n g i o t e n s i n a s e A, 280
A n g i o t e n s i n o g e n , 7
A n t i p l a s m i n , 405
A n t i t h r o m b i n I I I , 127, 555
A p r o t i n i n , 399, 509, 542, 566
A r a c h i d o n i c a c i d m e t a b o l i t e s ,
226
A r g i n y l a t i o n , 159
A r t i c u l a r c a r t i l a g e , 523
A r y l s u l f a t a s e , 4 1 2 , 520
A s c i t e s , 555
A s p a r t i c P r o t e i n a s e , 1
A s t r o c y t e s c u l t u r e , 200
A t r i a l n a t r i u r e t i c f a c t o r , 16
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A u t o p h a g y , 166
A z o c a s e i n , 141
B e t a - g a l a c t o s i d a s e , 412
B e t a - g l u c u r o n i d a s e , 3 99, 412,
520
B e t a - l - a n t i c o l l a g e n a s e , 42
B e t a - D - g l u c u r o n i d a s e , 46
B i o i n c o m p a t i b i l i t y , 365
B o w m a n - b i r k - i n h i b i t o r . 110
B r a c ' y k i n i n , 15
B r o n c h i a l P r o t e i n a s e
i n h i b i t o r , 115
B r o n c h o a l v e o l a r l a v a g e ,
137, 351
B u r n i n j u r y , 499
C a l p a i n , 175
C a n c e r , 8, 547
C a p t o p r i l , 13
C a r b o x y p e p t i d a . . e , 160
C a r d i o p l e g i a , 399
C a r d i o p u l m o n a r y b y p a s s ,
3 9 1 , 405
C a r t i l a g e i n h i b i t o r , 536
C a s e i n, 6
C a t a b o l i c f a c t o r s , 315
C a t h e p s i n
A, 160
B, 243, 245, 285, 306, 413
D, 3, 412, 520
E , 3
G, 23, 98, 123, 474, 525
L, 289, 306
C h e m i l u m i n e s c e n c e , 57, 378,
442
C h r o n i c r e n a l f a i l u r e , 3 4 5,
361
Chymase, 133
C h y m o s i n , 3
C h y m o t r y p s i n , 75
A, 97
- l i k e p r o t e a s e s , 97
C h y m o t r y p s i n i n h i b i t o r , 134
^ - i n h i b i t o r , 434
C o a g u l o p a t h y , 557
C o l l a g e n , 33
C o l l a g e n a s e , 33
C o l o n , 103
C o l o r e c t a l C a n c e r , 561
Complement, 365
c o m p o n e n t s , 226
C u p r o p h a n e , 3 7 3 , 377
C y c l o s p o r i n A, 293
C y s t e i n e p r o t e i n a s e s , 1 6 1 ,
175, 215
C y t o c h r o m e C, 378
C y t o k i n e s , 177
C y t o l y s i s , 539
C y t o l y t i c a c t i v i t y , 539
C y t o l y t i c T l y m p h o c y t e l i n e ,
535
D e r m i s , 89
D i g e s t i o n p r c d u c t s , 289
D i p e p t i d y l p e p t i d a s e , 351
I V , 207
D i p e p t i d y 1 a m i n o p e p t i d a s e , 160
I V , 278
Domain, 175
Duodenum, 103
E c t o e x o p e p t i d a s e , 45
E f f e c t i v e r e s p i r a t o r y
c o m p l i a n c e , 151
E g l i n C, 331
E l a s t a s e , 23, 42, 57, 149,
346, 3 78, 3 8 5 , 3 9 2 ,
445 , 4 5 7, 4 6 5 , 4 7 4 ,
4 8 1 , 4 8 5 , 519, 531
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E l a s t i n o l y s i s , 65
E l e c t r o n m i c r o g r a p h s , 300
Emphy sema, 107
E n a l a p r i l , 13
E n d o a m i n o p e p t i d a s e , 160
E n d o c y t i c v a c u o l e s , 289, 305
E n d o p e p t i d a s e , 13, 160, 161,
351
E n d o t o x i n , 4 2 5 , 474
E n k e p h a l i n a s e , 13
E p i d e r m i s , 89
Ex o g e n a l l e r g i c a l v e o l i t i s ,
137
E x o g l y c o s i d a s e s , 45
E x o p e p t i d a s e , 160
E x t r a c o r p o r e a l e x t r e m i t y
p e r f u s i o n , 565
F a c t o r H, 373
F i b r i n o l y s i s , 405
F i b r i n ( o g e n ) d e - j r a d a t i o n
p r o d u c t s , 405
F i b r o n e c t i n , 3 47, 555
G a m m a - g l u t a m y l t r a n s p e p t i d a s e ,
47, 276, 351
Gas e x c h a n g e , 150
G a s t r i c m ucosa, 102
G a s t r i e s i n , 1
G e l a t i n a s e , 33
G e l f i l t r a t i o n , 36
G e n t a m i c i n , 305
G l o m e r u l a r d i s e a s e , 267
G l o m e r u l a r p r o t e a s e s , 275
G l o m e r u l o n e p h r i t i s , 280
G l u c o c o r t i c o i d s , 45, 257
G l u t a m y l a m i n o p e p t i d a s e , 351
G r a n u l o e y t e s , 465
H - D - P r o - P h e - A r g - c h l o r o m e t h y l
k e t o n e , 540
H e m o d i a l y s i s , 245, 377
H e p a t o c y t e s , 159, 176, 186,
191
H e p a t o c y t e - s t i m u l a t i n g
f a c t o r , 191
Hepatome, 207
H e t e r o l y s o s o m e s , 284, 305
H i g h m o l e c u l a r mass
p r o t e i n a s e s , 216
H i s t a m i n e , 1 33, 509
H i s t o c h e m i c a 1 t o x i c o l o g y , 45,
H i s t o c h e m i s t r y , 351
Human P r o t e i n a s e i n h i b i t o r ,
123
Human s e c r e t o r y l e u k o c y t e
p r o t e a s e i n h i b i t o r , 123
H y d r o p h o b i c i t y , 159
H y d r o x y p r o l i n e , 145
H y p o t h e r m i a , 399
I d i o p a t h i c p u l m o n a r y
f i b r o s i s , 137
IgG s p l i t p r o d u c t s , 531
I m m u n o h i s t o c h e m i c a 1 s t a i n i n g ,
211
I m m u n o l o c a l i z a t i o n , 210
I m m u n o s u p p r e s s i o n , 385
I n f l a m m a t i o n , 465
I n f l a m m a t o r y d i s e a s e s , 505
I n f l a m m a t o r y J o i n t d i s e a s e s ,
523
I n j u r y s e v e r i t y s c o r e , 422
I n s u l i n , 421
r e e e p t o r , 239
r e s i s t a n c e , 315
I n t e r f e r o n ß, 191
I n t e r l e u k i n - 1 , 1 9 1, 225
I n t e r s t i t i a l l u n g d i s e a s e , 1 3 7
I n t e r s t i t i a l l u n g f i b r o s i s ,
145
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I n t e r - a l p h a - t r y p s i n -
i n h i b i t o r , 75, 89
K a l l i k r e i n , 172, 4 5 3 , 499
K i d n e y , 275, 295
s e c t i o n s , 277
t r a n s p l a n t a t i o n , 309
K i n i n a s e , 13
K i n i n o g e n s , 175, 3 6 1 , 501
K u p f f e r c e l l s , 193
K w a s h i o r k o r , 413
L a m i n i n , 268
L e u k o c y t e e l a s t a s e , 107, 115,
128, 435
L e u p e p t i n , 324, 515
Long c h a i n f a t t y a c i d s , 216
Lung e l a s t i n , 107, 115
L y s o s o m a l
enzymes , 519
h y d r o l a s e s , 2.6
p r o t e a s e s , 283, 305
L y s o s o m e s , 160, 284, 305
L y s o z y m e , 226
M a c r o p h a g e s , 193, 425
M a g n e s i u m , 299
M a l i g n a n t t u m o r , 551
M a l n u t r i t i o n , 411
M arasmus, 413
M a s t c e l l s , 133
Melanoma, 566
M e n i n g i t i s , 485
M e p r i n , 293
M e t a b o l i e a c i d o s i s , 318
M e t a l l o e n d o p e p t i d a s e , 13
M e t a l l o p r o t e i n a s e , 33, 293
M e t h y l c a s e i n , 217
M o n o c l o n a l a n t i b o d i e s , 207
M o n o c y t e s , 193, 425
M o n o c y t e - d e r i v e d f a c t o r , 191
M o n o k i n e s , 226
M o n o n u c l e a r p h a g o c y t e s , 225
M u l t i c a t a l y t i c P r o t e i n a s e ,
216
M u s c l e p r o t e i n t u r n o v e r , 225
M u s c l e p r o t e o l y s i s , 318
M y o f i b r i l l a r P r o t e i n a s e , 263
N - a c e t y l g l u c o s a m i n i d a s e , 4 0 2 ,
4 1 3 , 450
N-end r u i e , 161
N e o p t e r i n , 461
N e p h r o t o x i c n e p h r i t i s , 267
N e u r o t e n s i n , 15
N e u t r a l p r o t e a s e s , 226
N e u t r o p h i l e l a s t a s e , 27, 28,
65, 75, 123
N i t r o g e n b a l a n c e , 323
N o n - l y s o s o m a l p r o t e a s e s , 235
N t - m e t h y l - h i s t i d i n e , 262,
328, 336
N u t r i t i o n , 411
O l e i c a c i d , 219
0 1 e o y 1 - c o e n z y m e A, 220
O p s o n i n s , 441
O u c h t e r l o n y d o u b l e d i f f u s i o n
a s s a y , 185
O v e r n u t r i t i o n , 415
Oxygen r a d i c a l , 474
O x y t o c i n , 15
P a n c r e a t i c e l a s t a s e , 27
P a n c r e a t i c e l a s t a s e 2, 97
P a n c r e a t i c s e c r e t o r y t r y p s i n
i n h i b i t o r , 1 0 1 , 4 9 3 , 5 0 5 ,
547
P a n c r e a t i t i s , 245
P a p a i n , 161, 175
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P a r a t h y r o i d hormone, 257
P a r a t h y r o i d e c t o m y , 257
P e n i c i l l i n o p e p s i n , 5
P e p s i n o g e n , 1
P e p s i n s , 1
P e r i t o n i t i s , 4 3 3 , 441
P e r o x i d a t i o n , 449
P h o s p h a t a s e s , 45
P h o s p h a t i d y l - c h o l i n e , 220
P h o s p h a t i d y l - D , L - g l y c e r o l ,
220
P h o s p h a t i d y l - i n o s i t o l , 113
P h o s p h o l i p a s e C, 212
P h o s p h o r a m i d o n , 13
P h y s i c a l e x e r c i s e , 57
P l a s m i n , 172, 4 7 3 , 481
P l a s m i n o g e n , 347, 4 0 5 , 512,
555
P M N - F l a s t a s e , 499, 525
P n e u m o n i a , 19
P o l y g u a n y l i c ac d , 65
P o l y n u c l e o t i d s , 65
P o l y r i b o s y l r i b i t o l
P h o s p h a t a s e , 73
P r e k a l l i k r e i n , 347, 500
P r e p r o e l a s t a s e , 27
P r o s t a g l a n d i n E2, 225
P r o t e a s e , 238
P r o t e i n d e g r a d a t i o n , 317
P r o t e i n s p l i t p r o d u c t s , 339
P r o t e i n u r i a , 283, 267
P r o x i m a l t u b u l e , 283
P r o x i m a l t u b u l e c e l l s , 300
P u l m o n a r y v a s c u l a r
r e s i s t a n c e , 151
R a t
b r a i n , 199
l i v e r , 199, 207
R e a c t i v e o x y g e n , 226
R e n i n , 3, 361
R e s p i r a t o r y t r a c t , 123
R h e u m a t o i d
a r t h r i t i s , 107
J o i n t d e s t r u c t i o n , 526
s y n o v i a l f l u i d , 531
RNA h o m o p o l y m e r s , 71
RNAse, 520
S a l i c y 1 i c a c i d , 45
S a r c o i d o s i s , 137, 145
S e m i n a l p l a s m a i n h i b i t o r , 116
S e p s i s , 309, 339, 494, 517
S e p t i c e m i a , 485
S e p t i c s h o c k , 481
S e q u e n c e h o m o l o g y , 27
S e r i n e
e n d o p e p t i d a s e , 536
P r o t e i n a s e , 535
P r o t e i n a s e i n h i b i t o r , 523
S e r p i n s , 174
S h o c k , 449 , 481
S k e l e t a l m u s c l e , 215, 243
S k i n , 89
S t a r v a t i o n , 411
S t e a r o y 1 - coenzyme A, 220
S t e a r o y l - L - c a r n i t i n e , 220
S u b s t a n c e P, 15
S y n o v i a l f l u i d , 519
T h i o r p h a n , 13
T h r o m b i n , 4 7 3 , 481
T 1 y m p h o c y t e s , 539
T rauma, 309, 339
T r a u m a t i c i n j u r i e s , 519
T r i c h l o r a c e t i c a c i d , 339
T r y p s i n , 75, 525
T r y p s i n i n h i b i t o r , 134
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T r y p t a s e , 133
Tubulär p r o t e a s e s , 275
T u b u l e l u m e n , 289, 305
Tumor n e c r o s i s f a c t o r , 191
T u r n o v e r , 160
Type IV c o l l a g e n , 268
T y r o s i n e , 240
U b i q u i t i n a t i o n , 161
U l c e r s , 8
Urea-N a p p e a r a n c e , 259
U r e m i a , 315
U r e m i c
c a t a b o l i s m , 323
p a t i e n t s , 246
r a t s , 257
U r i n a r y P r o t e i n a s e a c t i v i t y ,
309
U r i n a r y p r o t e i n a s e s , 267
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