Particles binding beta(2)-integrins mediate intracellular production of oxidative metabolites in human neutrophils independently of phagocytosis

Complement-opsonised particles are readily ingested by human neutrophils th rough a complement receptor-mediated process leading to phagolysosome fusio n and production of oxidative metabolites. To investigate the complement re ceptor 3 (CR3)-associated signal system involved, cells were challenged wit h protein A-positive, heat-killed Staphylococcus aureus to which antibodies with specificity for the subunits of the beta(2)-integrins, i.e. anti-CD11 b (the alpha subunit of CR3) and anti-CD18 (the beta subunit of CR3), were bound through their Fc moiety. Despite not being ingested by the neutrophil s, the surface associated anti-CD18- and anti-CD11b-coated particles were a ble to activate the neutrophil NADPH-oxidase. Also antiCD11a- (the alpha su bunit of LFA-1) and to a lesser extent anti-CD11c- (the alpha subunit of CR 4) coated particles were able to trigger the NADPH-oxidase. The NADPH-oxida se was activated without extracellular release of reactive oxygen species. The activity was inhibited by cytochalasin B, suggesting a necessary role f or the cytoskeleton in the signalling pathway that activates the oxidase. W e show that particle-mediated cross-linking of beta(2)-integrins on the neu trophil surface initiates a signalling cascade, involving cytoskeletal rear rangements, leading to an activation of the NADPH-oxidase without phagosome formation or extracellular release of reactive oxygen species. (C) 1999 El sevier Science B.V. All rights reserved.