Serhan C N, Lundberg U, Weissmann G, Samuelsson B
Prostaglandins. 1984 Apr;27(4):563-81. doi: 10.1016/0090-6980(84)90092-3.
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.
尿酸单钠（MSU）晶体可刺激人类中性粒细胞和血小板生成花生四烯酸代谢产物。暴露于MSU的中性粒细胞从内源性花生四烯酸生成白三烯B（LTB）、6-反式-LTB4、12-表-6-反式-LTB4和5S，12S-二羟二十碳四烯酸（DHETE）。除了这些代谢产物外，暴露于MSU的中性粒细胞还形成了单羟基二十碳四烯酸（即5-羟二十碳四烯酸，5-HETE）和ω-氧化产物（即2-氧代-羧基-LTB4）。添加外源性花生四烯酸会导致这些代谢产物的生成增加。当中性粒细胞用秋水仙碱（10微摩尔）处理时，LTB4的形成受到损害，但5-HETE的形成不受影响。暴露于MSU的（1-14C）花生四烯酸标记的血小板释放出（1-14C）-花生四烯酸、（14C）-12-羟二十碳四烯酸（12-HETE）、（14C）-12-羟基-5,8,10,14-二十碳四烯酸（HHT）和（14C）-血栓素B2。结果表明，MSU刺激人类中性粒细胞和血小板中的花生四烯酸代谢。此外，这些结果不仅表明花生四烯酸的代谢产物可能被视为晶体相关疾病中炎症介质的可能候选物，而且秋水仙碱可阻断LTB4的形成。
