The third component of complement (C3) bound to tumor target cells enhances their sensitivity to killing by activated macrophages.
The third component of complement (C3) bound to P815 tumor cells enhanced their susceptibility to killing by Corynebacterium parvum-activated murine macrophages (M phi). Hemolytically active normal mouse serum and C5-deficient mouse serum were used to deposit complement (C) on P815 tumor cells, in the absence of exogenous antibody, by an alternative pathway mechanism. Cell-bound C3 was detected and was quantified by using a cellular enzyme-linked immunospecific assay. Activated M phi produced tumor cytolysis in a serum-free 16-hr 51Cr-release assay. The lysis of C-treated tumor cells was increased over targets treated with sera containing 10 mM EDTA, heat-inactivated mouse sera, or medium. In addition, C alone did not cause specific 51Cr release. M phi elicited by casein or PBS did not lyse any of the tumor targets tested. The increase in lysis was dependent on the dilution of serum used, and was strongly correlated with the amount of C3 detected on the tumor cells. The enhanced lysis was abrogated by incubating C3-bearing tumor cells with F(ab')2 fragments of a goat anti-mouse C3 antibody. C treatment did not alter the kinetics of tumor cell lysis, nor did it enhance the binding of the targets to effector cells. These results suggest that C may regulate M phi-mediated killing of tumor cells by increasing the lytic efficiency of M phi that are in contact with target-bound C3.
D000818:Animals; D003176:Complement C3 / Q000494:pharmacology*; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D012515:Mast-Cell Sarcoma / Q000473:pathology*; D051379:Mice; D008806:Mice, Inbred AKR / Q000276:immunology; D008809:Mice, Inbred C3H / Q000276:immunology
D003176:Complement C3; C042295:complement C5b-8 complex; D003165:Complement System Proteins