PHOSPHOLIPID SOURCES OF METABOLICALLY ELONGATED GAMMA-LINOLENIC ACID - CONVERSION TO PROSTAGLANDIN-E(1) IN STIMULATED MOUSE MACROPHAGES
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We have previously demonstrated that macrophages possess an active long chain polyunsaturated fatty acid elongase capable of converting (>85%) gammalinolenic acid (18:3n-6, GLA) to dihomogammalinolenic acid (20:3n-6, DGLA), which, following cell stimulation, is converted to prostaglandin E1 (PGE1) (Chapkin, R.S. and Coble, K.J. (1991). Biochimica et Biophysica Acta 1085, 365-370). This is noteworthy because PGE1 is an eicosanoid with anti-aggregatory and anti-inflammatory properties. In the present study, mouse peritoneal macrophages were incubated with [14C]GLA and [3H]-glycerol for 20 hr and subsequently stimulated with calcium ionophore A23187 (phospholipase A2 activator), phorbol ester (PMA, protein kinase C activator), PMA + A23187, merthiolate (lysophospharide acyltransferase inhibitor) + A23187, or nothing. Following stimulation, PMA + A23187 and merthiolate + A23187 treated cells had significantly (P < 0.05) increased levels of [14C-(PGE1) and [14C]-prostaglandin E2 (PGE2) biosynthesis compared with A23187, PMA, and nonstimulated treatments. [14C]-fatty acid (primarily DGLA) was primarily incorporated into phosphatidylcholine (PC) (64.8 1.3%, in nonstimulated cells). A23187, PMA, PMA + A23187, and merthiolate + A23187 treatments had significantly (P < 0.05) decreased levels of [14C]-PC and increased (P < 0.05) levels of [3H]-lyso-PC relative to nonstimulated cells. Therefore, in vitro activation of phospholipase A2 and inhibition of [14C]DGLA (derived from [14C]GLA) reacylation can significantly (P < 0.05) enhance [14C]-(PGE1) biosynthesis. These data indicate the regulatory importance of [14C]DGLA reacylation relative to phospholipase A2 activity in mouse peritoneal macrophage PGE1 biosynthesis. 1993.