Chemokines regulate cellular polarization and adhesion receptor redistribution during lymphocyte interaction with endothelium and extracellular matrix. Involvement of cAMP signaling pathway.

摘要: Leukocyte recruitment is a key step in the inflammatory reaction. Several changes cell morphology take place during lymphocyte activation and migration: spheric-shaped resting T cells become polarized activation, developing well defined cytoplasmic projection designated as cellular uropod. We found that chemotactic proinflammatory chemokines RANTES, MCP-1, and, to lower extent, MIP-1 alpha, beta, IL-8, were able induce uropod formation ICAM-3 redistribution lymphoblasts adhered ICAM-1 or VCAM-1. A similar chemokine-mediated effect was observed binding fibronectin fragments of 38- 80-kD, contain sites for integrins VLA-4 VLA-5, respectively. The structure concentrated adhesion molecule (a ligand LFA-1), emerged outer milieu from area contact between protein ligands. In addition, we other molecules such ICAM-1, CD43, CD44, also redistributed upon RANTES stimulation, whereas wide number surface receptors did not redistribute. Chemokines displayed selective among different subsets; beta had more potent action on CD8+ tumor infiltrating lymphocytes (TIL), alpha targeted selectively CD4+ cells. have examined involvement cAMP signaling pathway formation. Interestingly, several agonists redistribution, H-89, specific inhibitor cAMP-dependent kinase, abrogated formation, thus pointing out role development this projection. Since induced by completely Bordetella pertussis toxin, membrane appears be dependent G proteins pathways. myosin-based cytoskeleton response suggested prevention phenomenon with myosin-disrupting agent butanedione monoxime. inhibited ICAM-3-mediated aggregation, but substrata. Altogether, these results demonstrate receptor novel function mediated chemokines; may represent mechanism significantly contributes circulating leukocytes foci.