Decreased Fc and C3 receptor function in macrophage populations which are refractory to migration inhibitory factor, C3 activators, and immune complex.
Guinea pig macrophage populations previously established to be either responsive or refractory to activation by migration inhibitory factor (MIF) and Lotus fucolectin in the macrophage migration inhibition (MMI) assay were further characterized for their MMI response to diverse effectors as correlated with their Fc and C3b receptor function. MIF-refractory populations were found to be uniformly unresponsive to the complement activators: bacterial lipopolysaccharide, cobra venom factor, zymosan, and immune complex. MIF-responsive macrophages were responsive to the same activators. Fc-mediated binding and phagocytosis of IgG-coated sheep erythrocytes (EA) were markedly depressed in freshly harvested refractory macrophages as compared to responsive cells. Fc phagocytosis by refractory populations increased rapidly during 24-28 hr in vitro culture to levels equal to that of responsive cells which corresponded with an increase in their MMI response to MIF. Refractory macrophages also had decreased C3b receptor function as shown by reduced binding and phagocytosis of EAC or serum-coated zymosan and displayed a greater loss in C3b binding capacity than responsive cells during 48 hr in vitro culture. Trypsinization of responsive macrophages rendered them refractory in their MMI response to the various activators and selectively reversed C3b-dependent binding without effect on Fc binding. The plasmin esterase inhibitors, epsilon-amino-n-caproic acid, tranexamic acid, and L-lysine, previously established to reverse the MMI response to MIF, FBP, and C3 activators were found to inhibit both Fc- and C3-dependent phagocytosis. These results indicate that macrophage populations which are refractory to migration inhibition by MIF and C3 activators also have reduced Fc- and C3b-mediated phagocytic functions as compared to more mature responsive populations.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D002478:Cells, Cultured; D003166:Complement Activating Enzymes / Q000494:pharmacology*; D006168:Guinea Pigs; D037102:Lectins / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000494:pharmacology*; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000276:immunology*; D008297:Male; D010587:Phagocytosis / Q000187:drug effects*; D011951:Receptors, Complement / Q000276:immunology*; D011961:Receptors, Fc / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D037102:Lectins; D008263:Macrophage Migration-Inhibitory Factors; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D011961:Receptors, Fc; D003166:Complement Activating Enzymes; D014357:Trypsin