Chemokines trigger immediate β2 integrin affinity and mobility changes:: Differential regulation and roles in lymphocyte arrest under flow

Chemokines trigger rapid integrin-dependent lymphocyte arrest to Vascular endothelium. We show that the chemokines SLC, ELC, and SDF-1 alpha rapidly induce lateral mobility and transient increase of affinity of the beta2 integrin LFA-I. Inhibition of phosphatidylinositol 3-OH kinase (PI(3)K) activity blocks mobility but not affinity changes and prevents lymphocyte adhesion to ICAM-1 immobilized at low but not high densities, suggesting that mobility enhances the frequency of encounters between high-affinity integrin and ligand but that at higher ligand density affinity changes are sufficient for arrest. Thus, chemokines trigger, through distinct signaling pathways, both a high-affinity state and lateral mobility of LFA-1 that can coordinately determine the vascular arrest of circulating lymphocytes under physiologic conditions.