Formation of leukotrienes and hydroxy acids by human neutrophils and platelets exposed to monosodium urate

Abstract

Monosodium urate (MSU) crystals stimulate the production of arachidonic acid metabolites by human neutrophils and platelets. Neutrophils exposed to MSU generated leukotriene B 4(LTB 4). 6- trans -LTB 4, 12- epi -6- trans -LTB 4, and 5S, 12S DHETE from endogenous sources of arachidonate. In addition to these metabolites both monohyroxyeicosatetraenoic acids (i.e., 5-HETE) and w-oxidation products (i.e., 20-COOH LTB 4) 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 uM), LTB 4 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 B 2. 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 LTB 4.