C1Q TRIGGERS NEUTROPHIL SUPEROXIDE PRODUCTION BY A UNIQUE CD18-DEPENDENT MECHANISM

Complement protein C1q induces the production of superoxide (O-2(-)) b y neutrophils via an as yet unidentified receptor or receptor complex, Several strategies were therefore used to identify cell surface molec ules involved in the response of neutrophils to Clq and its collagen-l ike domain (Clq-CLR), Treatment of neutrophils with phosphatidylinosit ol-specific phospholipase C effectively removed the phosphatidylinosit ol-linked surface molecules CD14 and CD16, yet did not reduce O-2(-) p roduction in response to Clq, Next, 17 monoclonal antibodies (mAbs) re cognizing various neutrophil surface antigens were tested for their ab ility to inhibit Clq-CLR-mediated O-2(-) production, Only two of the m Abs, 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 prod uce O-2(-) in response to Clq or Clq-CLR, Because CDllb/CD18 is recogn ized to play a role in cell adhesion, the role of adherence in Clq-med iated O-2(-) production was explored. Adherence of neutrophils to C1q- CLR-coated surfaces occurred with kinetics, which usually paralleled t hose of O-2(-) production, and was invariably abolished by the anti-CD 11b mAb 44a. However, this mAb often only partially inhibited O-2(-) production, indicating that an avid attachment of neutrophils to the C lq-CLR-coated surface is not required for O-2(-) production.