title: Exogenous C1q reconstitutes a secondary deficiency of C5-deficient AKR mouse macrophages for FcR-dependent cellular cytotoxicity and phagocytosis.
abstract: Studies originally designed to assess the putative role of endogenous C5 in macrophage activation for antibody-dependent cellular cytotoxicity (ADCC) yielded unanticipated results. Resident and inflammatory peritoneal macrophages from C5-deficient AKR mice were found to have significantly lower capacity for FcR-dependent ADCC activation and phagocytosis of IgG-opsonized SRBC targets than did C5-competent C3HeB/FeJ (C3H) mice. Reconstitution of the ADCC response of AKR macrophages was accomplished initially with C5-sufficient C3H mouse serum, which suggested that endogenous C5 may be required for ADCC activation. However, further investigation largely eliminated C5 involvement in that a heat-labile component of C5-deficient AKR serum was shown to be active in the reconstitution of ADCC activation of AKR macrophages. Macrophages from AKR mice were found to have significantly lower levels of C1q mRNA synthesis, endogenous C1q levels, and C1q secretion than did C3H mouse macrophages as determined by Northern blot, Western blot, and presynthetic radiolabeling analysis, respectively. The addition of purified exogenous C1q to IgG-opsonized SRBC targets fully reconstituted ADCC activation for AKR inflammatory peritoneal macrophages to levels of normally FcR-responsive C3H macrophages. Similarly, exogenous C1q augmented FcR-dependent phagocytosis of AKR macrophages but had no effect on macrophages from responsive C3H mice. Our results indicate that AKR mice have a deficiency for FcR-dependent cellular cytotoxicity and phagocytosis that is related to their low potential for C1q synthesis and secretion rather than to their established genetic deficiency for C5 synthesis. We tentatively conclude that endogenous C1q is required as an accessory molecule for macrophage FcR-dependent effector functions and that C5 is not a prerequisite for ADCC activation.
authors.affiliation: Biomedical Division, Samuel Roberts Nobel Foundation, Inc., Ardmore, OK 73402.
authors.forename: R W
authors.initials: RW
authors.lastname: Leu
authors.forename: A Q
authors.initials: AQ
authors.lastname: Zhou
authors.forename: M J
authors.initials: MJ
authors.lastname: Kennedy
authors.forename: B J
authors.initials: BJ
authors.lastname: Shannon
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D015922:Complement C1q / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D003182:Complement C5 / Q000172:deficiency*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D010587:Phagocytosis; D011961:Receptors, Fc / Q000502:physiology
chemical_list: D003182:Complement C5; D011961:Receptors, Fc; D015922:Complement C1q