Chemokines trigger immediate beta 2 integrin affinity and mobility changes: Differential regulation and roles in lymphocyte arrest under flow

Chemokines trigger rapid integrin-dependent lymphocyte arrest to Vascular e ndothelium. We show that the chemokines SLC, ELC, and SDF-1 alpha rapidly i nduce lateral mobility and transient increase of affinity of the beta2 inte grin LFA-I. Inhibition of phosphatidylinositol 3-OH kinase (PI(3)K) activit y blocks mobility but not affinity changes and prevents lymphocyte adhesion to ICAM-1 immobilized at low but not high densities, suggesting that mobil ity enhances the frequency of encounters between high-affinity integrin and ligand but that at higher ligand density affinity changes are sufficient f or arrest. Thus, chemokines trigger, through distinct signaling pathways, b oth a high-affinity state and lateral mobility of LFA-1 that can coordinate ly determine the vascular arrest of circulating lymphocytes under physiolog ic conditions.