Leukotriene B/sub 4/ modulates human polymorphonuclear leukocyte (PMN) phospholipid (PL) methylation

Formation of phosphatidylcholine (PC) by methylation of phosphatidylethanolamine (PE) is required for transduction of chemotactic factor messages in phagocytic cells, including the development of a motile configuration and release of arachidonic acid (AA) from PL. The authors examined PL methylation in human peripheral blood PMN following stimulation by leukotriene B/sub 4/ (LTB/sub 4/), a potent chemotactic lipid metabolite of AA that is produced by human PMN. (/sup 3/H)-methionine, in the presence or absence of LTB/sub 4/, was added directly to the cells without a preloading period. (/sup 3/H)-methyl mono- and di-methylated PE, PC and lyso PC were separated by thin layer chromatography. PL methylation in human PMN is dependent on time of incubation, LTB/sub 4/ concentration and methionine concentration. The optimal LTB/sub 4/ concentration is 10/sup -7/ M, the same concentration that induces a maximal chemotactic response in PMN. At early time points (2-10 min), formation of methylated PL is enhanced following LTB/sub 4/ stimulation. In contrast, at later time points (20-60 min), methylated PL synthesis in LTB/sub 4/ treated cells is depressed or the same as control cells. Synthesis of PC by the choline transferase pathway is not affected by LTB/sub 4/ stimulation. This data shows that, at earlymore » time points following LTB/sub 4/ stimulation, PL methylation is enhanced. This correlates with other reports of calcium mobilization and chemotaxis in PMN at early time points following LTB/sub 4/ stimulation.« less