Modulation of FcR function by complement: subcomponent C1q enhances the phagocytosis of IgG-opsonized targets by human monocytes and culture-derived macrophages.
We have investigated the interaction of C1q, a subunit of the first component of complement, with human monocytes and culture-derived macrophages. Adherence of these mononuclear phagocytes to surfaces coated with C1q induced a marked enhancement of the phagocytosis of sheep erythrocytes opsonized with IgG anti-Forssman antibody (EA-IgG). This C1q-mediated enhancement of phagocytosis was dose dependent, and was specifically blocked by pretreatment of the C1q-coated surfaces with F(ab')2 anti-C1q. The augmentation of FcR-mediated phagocytosis by C1q was determined to be a result of the interaction between the C1q and the phagocytic effector cell, and was not due to interaction between the surface-bound C1q and the EA-IgG. Neither resting nor N-formyl-methionyl-leucyl-phenylalanine-stimulated polymorphonuclear leukocytes were induced by C1q to increase FcR-mediated phagocytosis. Experiments conducted with purified fragments of C1q suggest that the C1q phagocytosis enhancement signal resides in the collagen-like tail domain of the molecule. This region is the same portion of the molecule previously shown to interact with the cell surface C1q receptor. Native type I collagen was unable to enhance FcR-mediated phagocytosis by mononuclear phagocytes. It has been demonstrated that C1q can be localized to areas of inflammation, and additionally C1q can be secreted by macrophages in culture. In view of these findings and the results of our present study, we hypothesize that C1q could provide local, direct, and non-opsonic enhancement of phagocytosis by mononuclear phagocytes in areas of infection and inflammation.
D002448:Cell Adhesion / Q000187:drug effects; D003166:Complement Activating Enzymes / Q000494:pharmacology*; D003172:Complement C1 / Q000494:pharmacology*; D015922:Complement C1q; D003171:Complement Pathway, Classical; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects*; D011961:Receptors, Fc / Q000502:physiology*
D003172:Complement C1; D007140:Immunoglobulin Fab Fragments; D011961:Receptors, Fc; D015922:Complement C1q; D003166:Complement Activating Enzymes