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 (HETEs) on the synthesis of leukotriene C4 (LTC4), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) by mouse resident peritoneal macrophages incubated with zymosan particles (100 micrograms/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 = 1.1 microM) and TXB2 (IC50 = 38.9 microM) synthesis; in contrast, 15-HETE induced a consistent but variable enhancement of PGE2 synthesis. 5-HETE (IC50 = 15 microM), 5-lactone HETE (IC50 = 10.4 microM) and 12-HETE (IC50 = 13 microM) also inhibited LTC4 synthesis but they were approximately an order of magnitude less potent than 15-HETE. Furthermore, 5-HETE, 5-lactone HETE and 12-HETE inhibited TXB2 (IC50 = 20.4, 16.9 and 11.8 microM, respectively) and PGE2 (IC50 = 38.6, 2.3 and 11.6 microM, respectively) synthesis. Thus, monoHETEs exert modulatory actions on arachidonic acid metabolism and the different isomers of HETE differ quantitatively and qualitatively in their actions.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D015232:Dinoprostone; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D011458:Prostaglandins E / Q000096:biosynthesis; D013189:SRS-A / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis; D015054:Zymosan / Q000494:pharmacology
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D011458:Prostaglandins E; D013189:SRS-A; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D015054:Zymosan; D015232:Dinoprostone