C1q triggers neutrophil superoxide production by a unique CD18-dependent mechanism.
Complement protein C1q induces the production of superoxide (O2-) by neutrophils via an as yet unidentified receptor or receptor complex. Several strategies were therefore used to identify cell surface molecules involved in the response of neutrophils to C1q and its collagen-like domain (C1q-CLR). Treatment of neutrophils with phosphatidylinositol-specific phospholipase C effectively removed the phosphatidylinositol-linked surface molecules CD14 and CD16, yet did not reduce O2- production in response to C1q. Next, 17 monoclonal antibodies (mAbs) recognizing various neutrophil surface antigens were tested for their ability to inhibit C1q-CLR-mediated O2- production. Only two of the mAbs, 44a and IB4, which recognize CD11b/CD18 (complement receptor 3 or Mac-1), were inhibitory. In addition, neutrophils from a patient with leukocyte adhesion deficiency, which are CD18 deficient, did not produce O2- in response to C1q or C1q-CLR. Because CD11b/CD18 is recognized to play a role in cell adhesion, the role of adherence in C1q-mediated O2- production was explored. Adherence of neutrophils to C1q-CLR-coated surfaces occurred with kinetics, which usually paralleled those of O2- production, and was invariably abolished by the anti-CD11b mAb 44a. However, this mAb often only partially inhibited O2- production, indicating that an avid attachment of neutrophils to the C1q-CLR-coated surface is not required for O2- production.
Goodman
E B
EB
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717, USA.
Anderson
D C
DC
Tenner
A J
AJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D018845:CD11 Antigens / Q000276:immunology / Q000502:physiology; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D015922:Complement C1q / Q000302:isolation & purification / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000097:blood* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013481:Superoxides / Q000097:blood*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D007074:Immunoglobulin G; D013481:Superoxides; D015922:Complement C1q; D003094:Collagen