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

Complement protein C1q induces the production of superoxide (O-2(-)) 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 Clq and its collagen-like domain (Clq-CLR), Treatment of neutrophils with phosphatidylinositol-specific phospholipase C effectively removed the phosphatidylinositol-linked surface molecules CD14 and CD16, yet did not reduce O-2(-) production in response to Clq, Next, 17 monoclonal antibodies (mAbs) recognizing various neutrophil surface antigens were tested for their ability to inhibit Clq-CLR-mediated O-2(-) 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 O-2(-) in response to Clq or Clq-CLR, Because CDllb/CD18 is recognized to play a role in cell adhesion, the role of adherence in Clq-mediated O-2(-) production was explored. Adherence of neutrophils to C1q-CLR-coated surfaces occurred with kinetics, which usually paralleled those 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 Clq-CLR-coated surface is not required for O-2(-) production.