PHOSPHOLIPID SOURCES OF METABOLICALLY ELONGATED GAMMA-LINOLENIC ACID - CONVERSION TO PROSTAGLANDIN-E(1) IN STIMULATED MOUSE MACROPHAGES
Academic Article
Overview
Research
Identity
Additional Document Info
Other
View All
Overview
abstract
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.
