CROSS-TALK BETWEEN CELL-ADHESION MOLECULES REGULATES THE MIGRATION VELOCITY OF NEUTROPHILS

Background: Although the adhesive mechanisms underlying the capture an d immobilization of circulating neutrophils in inflamed blood vessels have been well described, factors controlling the subsequent migration of neutrophils over and through the blood vessel endothelium are poor ly understood. Directional rearrangement of the actin cytoskeleton wit hin the neutrophil, along with modulation of integrin-mediated adhesio n, are necessary for neutrophil migration, Signals from chemotactic ag ents and from the adhesive substrate may regulate these processes, but little is known about their relative importance or their mode of inte gration. Results: We examined the kinetics of neutrophil migration aft er formyl tripeptide or platelet-activating factor was perfused over n eutrophils that were already rolling on the adhesion molecule P-select in, which was presented either on the surface of immobilized platelets or in purified form coated on glass capillaries. Upon activation, neu trophils stopped rolling, spread and began to migrate; each of these p rocesses was dependent on beta 2 integrin (CD11b/CD18), The rate of mi gration increased over a period of about 8 minutes and was modulated d irectly by both the P-selectin and the CD31 surface receptors. Antibod y blockade of either CD31 or P-selectin on platelets resulted in a red uction in the velocity of migration, and simultaneous blockade of both receptors reduced velocity further. Purified CD31 and P-selectin (but not a control adhesion molecule, ICAM-1) increased migration velocity in a concentration-dependent and additive manner that reconstituted t he migratory behaviour observed on platelets. Conclusions: These studi es show that binding of ligands to CD31 and/or P-selectin modifies the rate of integrin-supported neutrophil migration. This novel example o f 'cross-talk' between surface receptors suggests that cell adhesion m olecules might generally transduce accessory signals between adjacent cells to modify their migratory responses to chemotactic signals.