Einfluss der Chemokinpräsentation auf das Reaktionsmuster von Leukozyten

• Applicant: Professor Michael Sixt
• Subject Area: Cell Biology
• Term: from 2009 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 159587272

Chemokines orchestrate immune cell trafficking by inducing either directed or random migration and by activating integrins in order to support adhesion to surfaces. Our preliminary data suggest that the way how chemokines are presented within lymphatic organs determines these different responses. The chemokine receptor CCR7 that is expressed on naive T cells and activated dendritic cells has two ligands: CCL19 and CCL2I, which differ in their ability to bind heparan sulfates. We found that the surface immobilized form of the heparan sulfate anchoring CCL2I caused random movement of dendritic cells that was confmed to the solid phase field by integrin mediated adhesion. Upon direct coniact with CCL21, dendritic cells proteolytically created a solubilized variant of CCL2I that formed a diffusion gradient. This fluid phase gradient triggered tactic movement but not integrin activation allowing the cells to move independent of surface adhesion. This reactivity pattem resembled CCL 19 that is not proteolytically processed. We want to address the molecular mechanisms ofthis proteolytic processing as well as its consequences for leukocyte trafficking within skin and lymph node.

• DFG Programme: Research Grants