Monoclonal antibodies binding to the human neutrophil C3bi receptor have disparate functional effects.
Three monoclonal antibodies (MAb)--OKMI, 7C3, and 60.3--immunoprecipitated a common 170-kd neutrophil membrane antigen closely associated with, or identical to, the C3bi receptor (CR3). Despite binding to a common receptor, these antibodies displayed marked differences in their effects on C3bi-mediated neutrophil function as assessed by the binding and ingestion of opsonized zymosan and the subsequent triggering of the respiratory burst. Antibody 7C3 caused a time-dependent, irreversible inhibition of the neutrophil oxidative response to opsonized zymosan that correlated with capping of the bound antibody. In contrast, antibody 60.3 caused an immediate inhibition of the neutrophil oxidative response to opsonized zymosan that required the continuous presence of exogenous antibody to achieve the maximal inhibitory effect. Antibody OKMI demonstrated minimal inhibition of O2- release. Despite their functional differences, binding of either 7C3 or 60.3 led to up-regulation of new antigen, presumably from intracellular sites as previously described using OKMI. Crossed immunoprecipitations of radiolabeled neutrophil lysates indicated that each MAb bound to different antigens near or within the CR3 complex. Thus three MAb binding to the neutrophil CR3 receptor each caused receptor up-regulation but had markedly different functional effects on the cell.
D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000302:isolation & purification / Q000502:physiology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005452:Fluoresceins; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D010101:Oxygen Consumption; D011233:Precipitin Tests; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D011951:Receptors, Complement / Q000378:metabolism*; D017463:Receptors, Complement 3b; D013481:Superoxides / Q000097:blood; D013861:Thiocyanates; D015054:Zymosan
D000911:Antibodies, Monoclonal; D005452:Fluoresceins; D011947:Receptors, Antigen, B-Cell; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D013861:Thiocyanates; D013481:Superoxides; D015054:Zymosan; D016650:Fluorescein-5-isothiocyanate