PULMONARY IMMUNOTOXICOLOGY

PULMONARY IMMUNOTOXICOLOGY

Edited by

Mitchell D. Cohen

Judith T. Zelikoff

Richard B. Schlesinger

New York University School of Medicine Department of Environmental Medicine

Tuxedo, New York, U.S.A .

.... " Springer Science+Business Media, LLC

Library of Congress Cataloging-in-Publication Data

Pulmonary immunotoxicology / edited by Mit.chell D. Cohen, Judith T. Zelikoff, Richard B. Schlesinger.

p.;cm. Includes bibliographical references and index. ISBN 978-1-4613-7046-8 ISBN 978-1-4615-4535-4 (eBook) DOI 10.1007/978-1-4615-4535-4 1.Pulmonary toxicology. 2. Immunotoxicology. 3. Respiratory allergy. 1. Cohen,

Mit.chell D., 1959- n. Zelikoff, Judith T. m. Schlesinger, Richard B. [DNLM: 1. Lung-drug effects. 2. Air Pollutants-adverse effects. 3. Immune

System-drug effects. 4. Lung-immunology. WF 600 P98349 2000] RC720 .P852ooo 616.2' 407-dc21

00-030161

Copyright O 2000 by Springer Science+Business Media New York Originally published by Kluwer Academic Publishers in 2000 Softcover reprint ofthe hardcover lst edition 2000

AlI rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, mechanical, photo­copying, recording, or otherwise, without the prior written permission of the publisher, Springer Science+Business Media, LLC.

Printed on acid-Iree pa per.

DEDICATION

I dedicate this book to the memory of my companions Vaska, Whitey, and Bebe.

M.D.C.

This book is dedicated to the research assistants and graduate students who helped build my laboratory. I also dedicate this book to my Mother and Sister who have always believed in me and provided support and encouragement during difficult times.

J.T.Z.

To my grandson Jack and the next generation of toxicologists.

R.B.S.

TABLE OF CONTENTS List of Contributors ............................................................................ .ix Preface ................................................................................................ xi Editors Profiles ................................................................................. xiii

Section I. The Respiratory Tract

Chapter 1 Comparative Structure of the Respiratory Tract: Airway Architecture in Humans and Animals ....................................................................... l Jack R. Harkema, Charles G. Plopper, and Kent E. Pinkerton

Chapter 2 Immunology of the Respiratory Tract.. .............................................. 61 Robert W. Lange and Meryl H. Karol

Chapter 3 Disposition of Inhaled Particles and Gases ........................................ 85 Richard B. Schlesinger

Section II. Adverse Effects of Altered Pulmonary Immunity

Chapter 4 Hypersensitivity and Asthma ........................................................... 107 M. Ian Gilmour

Chapter 5 Inflammation and Fibrosis ............................................................... 127 David J. P. Bassett and Deepak K. Bhalla

Chapter 6 Pulmonary Autoimmunity and Inflammation .................................. 153 Thomas M. Jeitner and David Lawrence

Section III. Immunotoxicants

Chapter 7 Biological Agents ............................................................................. 181 Robert L. Sherwood

Chapter 8 Pesticides, Solvents, and Polycyclic Agents .................................... 199 Kathleen E. Rodgers

viii Pulmonary Immunotoxicology

Chapter 9 Beryllium .......................................................................................... 213 Gregory L. Finch

Chapter 10 Arsenic, Cadmium, Chromium, and NickeL .................................. 241 Leigh Ann Bums-Naas

Chapter 11 Other Metals: Aluminum, Copper, Manganese, Selenium, Vanadium, and Zinc ......................................................................... 267 Mitchell D. Cohen

Chapter 12 Ozone ................................................................................................ 301 Lisa K. Ryan

Chapter 13 Sulfur and Nitrogen Oxides ............................................................. 337 Richard B. Schlesinger, Lung-Chi Chen, and Judith T. Zelikoff

Chapter 14 Asbestos and Silica .......................................................................... 353 David B. Warheit

Chapter 15 Woodsmoke, Kerosene Heater Emissions, and Diesel Exhaust. ............................................................................................ 369 Judith T. Zelikoff

Chapter 16 Tobacco Smoke ............................................................................... 387 Donald E. Gardner

Section IV. Risk Assessment

Chapter 17 Applying Pulmonary Immunotoxicity Data to Risk Assessment. .. .411 Mary Jane K. Selgrade

Chapter 18 Biomarkers of Pulmonary Immunologic Responses ...................... .433 Andrea K. Hubbard

Index ................................................................................................. 455

LIST OF CONTRIBUTORS David .I.P. Bassett, Department of Occupational and Environmental Health Sciences, Wayne State University, Detroit, MI42807

Deepak K. Bhalla, Department of Occupational and Environmental Health Sciences, Wayne State University, Detroit, MI 42807

Leigh Ann Burns-Naas, Toxicology and Product Safety, Health and Environmental Sciences, Dow Corning Corporation, Midland, MI 48611

Lung-Chi Chen, New York University School of Medicine, Depart­ment of Environmental Medicine, 57 Old Forge Road, Tuxedo, New York 10987

Mitchell D. Cohen, New York University School of Medicine, Department of Environmental Medicine, 57 Old Forge Road, Tuxedo, New York 10987

Gregory L. Finch, Inhalation Toxicology Laboratory, Lovelace Respiratory Research Institute, PO Box 5890, Albuquerque, NM 87185

Donald E. Gardner, Inhalation Toxicology Associates, Inc., P.O. Box 97605, Raleigh, NC 27624-7605

M. Ian Gilmour, Immunotoxicology Branch, Experimental Toxicol­ogy Division, National Health and Environmental Effects Research Laboratory, USEPA, Research Triangle Park, NC 27711

.lack R. Harkema, Department of Pathology, College of Veterinary Medicine, Institute for Environmental Toxicology, Michigan State University, East Lansing, MI 48824

Andrea K. Hubbard, Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269-2092

Thomas M . .leitner, Laboratory of Environmental and Clinical Immunology, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12201-509

Meryl H. Karol, Department of Environmental and Occupational Health, University of Pittsburgh, 260 Kappa Drive, Pittsburgh, PA 15238

x Pulmonary Immunotoxicology

Robert W. Lan2e, Department of Environmental and Occupational Health, University of Pittsburgh, 260 Kappa Drive, Pittsburgh, PA 15238

David Lawrence, Laboratory of Environmental and Clinical Immu­nology, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12201-509

Kent E. Pinkerton, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, Institute of Toxicology and Environmental Health, University of California, Davis, CA 95616

Charles G. Plopper, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, Institute of Toxicology and Environmental Health, University of California, Davis, CA 95616

Kathleen E. Rod2ers, University of Southern California, Livingston Research Institute, 1321 North Mission Road, Los Angeles, CA 90033

Lisa K. Ryan, Immunotoxicology Branch, National Health and Envi­ronmental Effects Research Laboratory, USEPA, Research Triangle Park, NC 27711

Richard B. Schlesin2er, New York University School of Medicine, Department of Environmental Medicine, 57 Old Forge Road, Tuxedo, New York 10987

MaryJane K. Sel2rade, National Health and Environmental Effects Research Laboratory, USEPA, Research Triangle Park, NC 27711

Robert L. Sherwood, Microbiology and Immunology Division, liT Research Institute, 10 West 35th Street, Chicago, IL 60616

David B. Warheit, DuPont Haskell Laboratory, 1090 Elkton Road, Newark, DE 19714

Judith T. Zelikoff, New York University School of Medicine, Department of Environmental Medicine, 57 Old Forge Road, Tuxedo, New York 10987

PREFACE

Within the toxicological sciences, pulmonary toxicology has been recognized as a specialized field of study for more than forty years, and immunotoxicology has been expanding since its inception in the early 1970s as a separate area of research. With increasing efforts in both areas, it is not unexpected that there would be a convergence of the two in the researchers' quests to understand how inhaled toxins and toxicants can affect human health. The area of pulmonary immunotoxicology has been very active over the past decade in attempting to elucidate how workplace and general environmental agents can produce changes in immunological function in the respiratory tract that may allow for alterations in health status.

The purpose of this book is to provide the Reader, in a single voluume, information concerning the effects of various inhaled materials upon the immune system of the respiratory tract. The book will be useful both to investigators in the field of pulmonary toxicology and immunotoxicology, as well as to those involved in administration and regulation of matters related to inhaled materials. It can also serve as a textbook for a course in pulmonary immuno­toxicology at the graduate or advanced undergraduate level.

The book is comprised of four sections. The first provides basic background concepts essential for understanding pulmonary immuno­toxicology. This includes discussions of the normal structure and function of the respiratory system, its basic immunology, and the manner by which inhaled particles and gases are removed from the air and deposit upon respiratory tract surfaces. The second section pro­vides an overview of the major types of pathological consequences which can arise from immunomodulation within the respiratory tract. These include hypersensitivity and asthma, inflammation and fibrosis, and immunosuppression and autoimmunity. The third section, which comprises the largest portion of the book, deals specifically with major classes of airborne agents that are known to alter immune function of the respiratory tract. These are arranged into major classes, i.e., organic agents, metals, gases, particles, biologics, and complex mixtures. The fourth and final section explores the area of risk assessment. This includes discussions of the basic concepts of risk assessment as they apply specifically to immunotoxicologic effects upon the lungs, and the use of biomarkers as indices of potential pulmonary immunotoxic responses to inhaled materials.

This is the first book which attempts to consolidate information evolving from the rapidly expanding field of pulmonary immuno­toxicology. As such, it is a valuable resource to those actively engaged in research in this area, as well as to those who may be thinking of entering the field. Because the book provides current information about many diverse agents in one readily accessible site, it may allow for some heretofore unseen linkages, such as mecha-

xii Pulmonary Immunotoxicology

nisms of action, to be made between these varied agents. Thus, the book is not only a review of what has been seen in the past, but also provides a starting point for what could be research agendas for the future.

Mitchell D. Cohen

Judith T. Zelikoff

Richard B. Schlesinger

Tuxedo, New York

EDITORS' PROFILES

Mitchell D. Cohen, Ph.D., is an Assistant Professor in the Depart­ment of Environmental Medicine of the New York University School of Medicine. Dr. Cohen received his B.S. in Chemistry and Physics from the State University of New York at Albany in 1981. He received his M.S. and Ph.D. degrees in Toxicology/Food Science and Human Nutrition in 1984 and 1988, respectively, from the University of Florida. Dr. Cohen then undertook two post-doctoral fellowships at the Nelson Institute for Environmental Medicine at the New York University School of Medicine; the first in the molecular toxicology of metals in the Laboratory for Molecular Toxicology and the second in the pulmonary immunotoxicology of inhaled environmental pollut­ant gases/metals/mixtures in the Laboratory of Pulmonary Biology and Toxicology.

Dr. Cohen is a member of several scientific societies including the Society of Toxicology, the Society for Leukocyte Biology, and American Association for Cancer Research. He has served on the editorial board for two toxicology journals, as well as on several society committees in the areas of Immunotoxicology and Inhalation Toxicology. Dr. Cohen has been involved in inmmunotoxicology research since 1981 and his research has involved investigations into the role(s) by which ambient and occupational pollutants may alter host resistance through modifications of immune cell cytokine receptor-cytokine interactions and biochemistry.

Judith T. Zelikoff, Ph.D., is an Associate Professor in the Department of Environmental Medicine of the New York University School of Medicine. She is currently President of the Immunotoxi­cology Specialty Section and Chairman of the Continuing Education Committee of the Society of Toxicology; she is also a member of the Inhalation and Metals Specialty Sections. Dr. Zelikoff has previously been an Editor on books in the areas of metal immunotoxicology and in ecotoxicology. Dr. Zelikoff is an Associate Editor for the journal Biomarkers and serves on editorial boards of several others including Toxicology, Toxicology and Applied Pharmacology, Journal of Toxi­cology and Environmental Health, and Aquatic Toxicology. She has organized several international conferences and workshops and has, as visiting scholar, lectured in many developing nations. Dr. Zelikoff has been involved in the area of pulmonary immunotoxicology for over 10 years. Her research interest is in discerning the role of indoor and outdoor airborne particulate mixtures in altering pulmonary host defense mechanisms against infectious disease-producing organisms.

xiv Pulmonary Immunotoxicology

Richard B. Schlesinger, Ph.D., is a Professor in the Department of Environmental Medicine of the New York University School of Medicine, where he is Director of the Systemic Toxicology Program. Dr. Schlesinger has served as President of the Inhalation Specialty Section of the Society of Toxicology, and was recepient of the Career Achievement Award from the Section in 1999. He has been recipient of an NIEHS Research Career Development Award and of the ILSI Kenneth Morgareidge Award for contributions to the field of inhalation toxicology. He has served on numerous national scientific committees, including those of EPA and NRC. His research involves investigations into the role which ambient and occupational air contaminants may play in the development of chronic nonneoplastic pulmonary disease.