Formation of leukotrienes and hydroxy acids by human neutrophils and platelets exposed to monosodium urate.
Monosodium urate (MSU) crystals stimulate the production of arachidonic acid metabolites by human neutrophils and platelets. Neutrophils exposed to MSU generated leukotriene B (LTB), 6-trans-LTB4, 12-epi-6-trans-LTB4, and 5S, 12S DHETE from endogenous sources of arachidonate. In addition to these metabolites both monohydroxyeicosatetraenoic acids (i.e., 5-HETE) and omega-oxidation products (i.e., 2O -COOH LTB4) were formed by neutrophils exposed to MSU. Addition of exogenous arachidonic acid led to increased formation of each of these metabolites. When neutrophils were treated with colchicine (10 microM), LTB4 but not 5-HETE formation was impaired. (1-14C)Arachidonate-labeled platelets exposed to MSU released (1-14C)-arachidonate, (14C)-12 HETE, (14C)-HHT and (14C)-thromboxane B2. Results indicate that MSU stimulates arachidonic acid metabolism in both human neutrophils and platelets. Moreover, they suggest not only that metabolites of arachidonate may be considered as possible candidates for mediators of inflammation in crystal-associated diseases, but that colchicine blocks the formation of LTB4.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids; D066298:In Vitro Techniques; D007536:Isomerism; D007975:Leukotriene B4 / Q000097:blood; D009504:Neutrophils / Q000378:metabolism*; D013929:Thromboxane B2 / Q000097:blood; D014527:Uric Acid / Q000494:pharmacology*
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; D014527:Uric Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid