MODULATION BY HYDROXYEICOSATETRAENOIC ACIDS (HETES) OF ARACHIDONIC-ACID METABOLISM IN MOUSE RESIDENT PERITONEAL-MACROPHAGES

The effects of 5-, 5-lactone, 12- and 15-hydroxyeicosatetraenoic acids (HETE) on the synthesis of leukotriene C4 (LTC4), thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) by mouse resident peritoneal macrophages incubated with zymosan particles (100 .mu.g/ml) were investigated. Zymosan phagocytosis stimulated a 110-, 16- and 16-fold increase in LTC4, TxB2 and PGE2 synthesis, respectively. 15-HETE inhibited zymosan-induced LTC4 (IC50 [concentration producing 50% inhibition] = 1.1 .mu.M) and TxB2 (IC50 = 38.9 .mu.M) synthesis; in contrast, 15-HETE induced a consistent but variable enhancement of PGE2 synthesis. 5-HETE (IC50 = 15 .mu.M), 5-lactone HETE (IC50 = 10.4 .mu.M) and 12-HETE (IC50 = 13 .mu.M) also inhibited LTC4 synthesis but they were approximately an order of magnitude less potent than 15-HETE. 5-HETE, 5-lactone HETE and 12-HETE inhibited TxB2 (IC50 = 20.4, 16.9 and 11.8 .mu.M, respectively) and PGE2 (IC50 = 38.6, 2.3 and 11.6 .mu.M, respectively) synthesis. MonoHETE exert modulatory actions on arachidonic acid metabolism and the different isomers of HETE differ quantitatively and qualitatively in their actions.