Transmethylation reactions regulate affinity and functional activity of chemotactic factor receptors on macrophages

Methylation mediated by S-adenosyl- l-methionine is required for the chemotaxis of mononuclear leukocytes. We investigated whether transmethylation reactions are required for normal functioning of chemotactic factor receptors. Three chemoattracrant-mediated functions in macrophages, chemotaxis, the stimulated release of arachidonic acid from membrane phospholipids and superoxide production, are markedly depressed by agents that inhibit cellular methylation reactions. Treatment of macrophages with methylation inhibitors decreased the affinity of the N-formylated chemoattractant receptor present on these cells by a factor of 4.5, but did not significantly alter the total receptor number. These results suggest that the N-formylated chemoattractant receptor on macrophages can exist in more than one affinity state and that an ongoing methylation reaction is required for the maintenance of the receptor in its higher affinity form. Inhibition of methylation lowers the affinity of the receptor and renders it no nfunctional or “uncoupled” in its ability to produce chemotaxis, superoxide and the release of arachidonic acid from leukocyte membranes.