Effects of inhibitors of C1q biosynthesis on macrophage Fc receptor subclass-mediated antibody-dependent cellular cytotoxicity and phagocytosis.
We examined the effects of the inhibitors of C1q or collagen biosynthesis, 2,2'-dipyridyl (DP), and 3,4-dehydro-DL-proline (DHP) on murine macrophage (M phi) FcR subclass-mediated antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis of sheep erythrocyte targets. Oil-elicited peritoneal M phi from C3HeB/FeJ mice which were cultured for 24 hr with DP (0.08 or 0.10 mM) or DHP (0.8 or 1.0 mM) showed a significant decrease in FcR subclass-mediated ADCC for murine monoclonal IgG2a (FcRI) and IgG2b/IgG1 (FcRII) as well as for heterologous polyclonal IgG. These collagen inhibitors also blocked phagocytosis mediated by both IgG2a- and IgG2b-opsonized erythrocytes. DP was more potent than DHP in blocking FcR effector functions in a reversible fashion and neither inhibitor affected M phi C3b receptor function. Pretreatment of M phi with collagenase resulted in significant reduction in FcR-mediated ADCC and phagocytosis. The inhibition of M phi FcR subclass-mediated ADCC and phagocytosis by collagen C1q synthetic inhibitors or by collagenase treatment further confirms a functional relationship between cell-associated C1q and FcR-dependent functions.
D015082:2,2'-Dipyridyl / Q000494:pharmacology*; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D003166:Complement Activating Enzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D003172:Complement C1 / Q000096:biosynthesis*; D003174:Complement C1 Inactivator Proteins; D015922:Complement C1q; D008264:Macrophages / Q000502:physiology / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D003012:Microbial Collagenase / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011961:Receptors, Fc / Q000276:immunology*
D003172:Complement C1; D003174:Complement C1 Inactivator Proteins; D011725:Pyridines; D011961:Receptors, Fc; C002195:3,4-dehydroproline; D015082:2,2'-Dipyridyl; D015922:Complement C1q; D011392:Proline; D003166:Complement Activating Enzymes; D003012:Microbial Collagenase