Modulation of phospholipid methylation in rabbit leukocytes by indomethacin.

Methylation of membrane phospholipids has been implicated as an early biochemical signal for the chemotactic migration of phagocytic cells into inflammatory sites. In this study, the ability of indomethacin to modulate phospholipid methylation as one of its mechanisms of antiinflammatory action was investigated. Nontoxic doses of indomethacin (10(-4) M and 10(-5) M) were found to retard the methylation of phosphatidylmonomethylethanolamine (PMME) to phosphatidyldimethylethanolamine (PDME) and phosphatidylcholine (PC) in rabbit leukocytes, suggesting inhibition of methyltransferase II activity. Indomethacin was, however, without effect on the uptake of L-[methyl 3H]methionine by rabbit leukocytes. It is suggested that the inhibition of membrane phospholipid methylation could result in the suppression of inflammatory responses such as prostaglandin and leukotriene synthesis, generation of reactive oxygen radicals, and chemotaxis.