marius döring zib class of 2009 paper presentation 14.02.2011
DESCRIPTION
Immobilized chemokine fields and soluble chemokine gradients cooperatively shape migration patterns of dendritic cells. - PowerPoint PPT PresentationTRANSCRIPT
Immobilized chemokine fields and soluble chemokine gradients
cooperatively shape migration patterns of dendritic cells
Kathrin Schumann, Tim Lämmermann,Markus Bruckner,Daniel F. Legler, Julien Polleux, Joachim P. Spatz,Gerold Schuler, Reinhold Förster, Manfred B. Lutz, Lydia Sorokin, and Michael Sixt
Marius DöringZIB Class of 2009paper presentation 14.02.2011
Introduction
Chemokines:
• chemotactic cytokines– Small 8-10 kDa– classification according to positioning of 4 cysteine residues– signal via GPCR
• central orchestrators of hematopoetic system– Homing & positioning of lymphocytes in secondary lymphoid organs– Integrin activation– Polarization of actomyosin cytoskeleton
Introduction
Cell movement
on a surface: • Haptokinesis vs haptotaxis
adhesion independent:• chemokinesis va chemotaxis
Chemotaxis Haptokinesis
Haptotaxis biased by chemotactic gradient
Model system:Migration of DC depentent on CCR7 and its ligands CCL19/21
CCL19:mostly soluble due to truncated N-terminus
CCL21:binds to heperansulfate
Adopted from Rot et. al 2008
Results
LPS matured DC on unfixed cryosection of inguinal LN
DCs mirgate on LN into the T cell area along the interfollicular region
Results
DCs mirgate on LN in a CCR7 & CCR7 ligand dependent manner along a soluble gradient
Results
Immobilized CCL21 triggers:1)rapid spreading2)random migration3)release of soluble factor to attract other DCs
Results
DCs generate a truncated CCL21 upon encouter of CCL21 by cleavage from the C terminus
Results
Haptokinesis (spreading, polarization & migration) of DCs is induced by interaction of CCR7 and immobilized ß2 integrin
Results
Chemotactic and adhesive signals compete & those two forces lead to a directed haptotactic movement
Conclusion• Mature DCs activated ß2 integrin and cytoskeletal
polarization upon contact with immonilized CCL21 haptokinetic movement
• CCL19 did not induce adhesion but cellular polarization chemotactic movement
• Combination of CCL19/21 lead to directionally biased haptokinetic migration
• During their mirgation DCs generated a truncated version of CCL21 – Immobiliezd CCL21 dictates the PW– Soluble factors direction of migration
The End
!!!Thank you for your attention!!!??Question??
Introduction