The role of transmethylation reactions in regulating the binding of BCG-activated murine macrophages to neoplastic target cells.
The ability of BCG-activated macrophages from C57BL/6J mice to lyse neoplastic targets was depressed by inhibitors of methyltransferase reactions (10(-4) M adenosine, 10(-5) M EHNA, and 10(-4) M L-homocysteine or 10(-5) M DZA). Binding of P815 mastocytoma targets to BCG-activated macrophages, which has been shown to be a necessary event in cytolysis of those targets, was also inhibited by adenosine, EHNA, and L-homocysteine or by DZA at the above concentrations. Inhibition of binding was obtained when macrophages were pretreated with the inhibitors, whereas pretreatment of targets with the inhibitors did not alter binding. The inhibitors were not toxic to the macrophages, as judged by morphology and viability of the macrophage cultures as well as by ability of macrophages to bind antibody-coated P815 targets or to secrete plasminogen activator. The inhibitors, at concentrations that inhibited cytolysis and binding, also depressed one type of S-adenosyl-L-methionine-mediated methylation reaction (protein carboxy-O-methylation) in BCG macrophages. The data suggest that transmethylation reactions are essential for the ability of BCG activated murine macrophages to bind and, hence, to destroy P815 tumor cells.
D000818:Animals; D000906:Antibodies; D001500:BCG Vaccine / Q000276:immunology*; D001665:Binding Sites; D003602:Cytotoxicity, Immunologic; D008264:Macrophages / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D011497:Protein O-Methyltransferase / Q000037:antagonists & inhibitors; D012513:Sarcoma, Experimental / Q000276:immunology*
D000906:Antibodies; D001500:BCG Vaccine; D008780:Methyltransferases; D011497:Protein O-Methyltransferase