The Metabolism of Leukotriene B4 in Lewis Lung Carcinoma Porcine Kidney Cells

摘要: Leukotriene B 4 [5(S), 12(R)-dihydroxy-6(Z),8(E),10(E),14(Z)-eicosatetraenoic acid, (LTB )] is a product of the 5-lipoxygenase pathway arachidonic acid metabolism operational in several cell types, including human polymorphonuclear leukocyte (1, 2). Because its purported biological function to mediate neutrophil infiltration, there considerable interest an understanding biosynthesis this eicosanoid during inflammatory reactions and, particular, lung. Several studies have shown that LTB can be biosynthesized challenged lung and measured bronchoalveolar lavage fluid (3-5). , like other eicosanoids, rapidly metabolized vivo by multiple pathways into biologically inactive products. Certain cells, leukocyte. are known express specific cytochrome P-450 (CYP4F3) carries out ω-oxidation form 20-hydroxy-LTB (6). (3-Oxidation predominant hepatocyte after initial methyl terminus alcohol dehydrogenase-mediated formation ω-carboxyl moiety (7, 8). enzymatic been discovered transform products, 12-hydroxyeicosanoid dehydrogenase (9) 10,11-reductase (10-12), which ultimately convert conjugated triene diene moiety. Most recently, glucuronide has described (13). Emergence electrospray tandem mass spectrometry facilitated (14, 15). This sensitive technique permits direct analysis metabolites as they separated eluted from high-performance liquid chromatography (HPLC) column. With implementation microbore HPLC columns, concentration maintained at high levels, ensuring maximal sensitivity spectrometric technique. While ionization generates abundant negative ions such carboxylate anion, provides structural information necessary characterize metabolites. Interest production within pulmonary tissue increased, but means one assess problematic because difficult organ sample. One strategy used for assessment prostaglandin measurement excreted urine (16). Rates endogenous LTC estimated measuring urinary LTE excretion (17). Therefore, identification stable markers more complete ultimate metabolic fate become interest. The eicosanoids intact organism could involve tissues, example, directly responsible subsequently enter circulation transported secondary site liver or kidney. Some studies, suggested exits once it enters (18), bring focus sites before urine.