NEUTROPHIL ROLLING, ARREST, AND TRANSMIGRATION ACROSS ACTIVATED, SURFACE-ADHERENT PLATELETS VIA SEQUENTIAL ACTION OF P-SELECTIN AND THE BETA(2)-INTEGRIN CD11B CD18/

Platelets bound to thrombogenic surfaces have been shown to support ac tivation-dependent firm adhesion of neutrophils in flow following sele ctin-mediated tethering and rolling, The specific receptor(s) responsi ble for mediating adhesion-strengthening interactions between neutroph ils and platelets has not previously been identified. Furthermore, the ability of adherent platelets to support the migration of bound neutr ophils has not been tested. We studied neutrophil interactions with ac tivated, surface-adherent platelets as a model for leukocyte binding i n vascular shear flow and emigration at thrombogenic sites. Our result s demonstrate that the beta(2)-integrin Mac-1 (CD11b/CD18) is required for both firm attachment to and transmigration of neutrophils across surface-adherent platelets. In flow assays, neutrophils from patients with leukocyte adhesion deficiency-1 (LAD-I), which lack beta(2)-integ rin receptors, formed P-selectin-mediated rolling interactions, but we re unable to develop firm adhesion to activated platelets, in contrast to healthy neutrophils, which developed firm adhesion within 5 to 30 seconds after initiation of rolling. Furthermore, the adhesion-strengt hening interaction observed for healthy neutrophils could be specifica lly inhibited by monoclonal antibodies (mAbs) to Mac-1, but not to lym phocyte function-associated antigen-1 (LFA-1; CD11a/CD18) or intercell ular adhesion molecule-2 (ICAM-2; CD102). Further evidence for a beta( 2)-integrin-dependent neutrophil/platelet interaction is demonstrated by the complete inhibition of interleukin (IL)-8-induced neutrophil tr ansmigration across platelets bound to fibronectin-coated polycarbonat e filters by mAbs to Mac-1. Thus, Mac-1 is required for firm adhesion of neutrophils to activated, adherent platelets and may play an import ant role in promoting neutrophil accumulation on and migration across platelets deposited at sites of vascular injury. (C) 1996 by The Ameri can Society of Hematology.