肝细胞在乙醇存在的情况下产生的趋化性白三烯B4代谢物。

Chemotactic LTB4 metabolites produced by hepatocytes in the presence of ethanol.

作者信息

Shirley M A, Reidhead C T, Murphy R C

机构信息

National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.

出版信息

Biochem Biophys Res Commun. 1992 Jun 15;185(2):604-10. doi: 10.1016/0006-291x(92)91667-f.

DOI:10.1016/0006-291x(92)91667-f

PMID:1319142

Abstract

Ethanol in low concentrations significantly alters the hepatocyte metabolism of the neutrophil chemotactic lipid leukotriene B4 (LTB4). Two novel metabolites of LTB4 which are encountered only when ethanol is present, retained significant biological activity. One metabolite, 3-hydroxy-LTB4 increased intracellular free calcium in the human neutrophil at concentrations as low as 3 x 10(-10) M as well as induced shape change and adherence to albumin-coated latex beads at 10 nM. The 3-hydroxy-LTB4 and 3,20-hydroxy-LTB4 metabolites were also potent chemotactic agonists with an ED50 at 3.0 and 9.0 nM, respectively. These results suggest that the presence of ethanol can substantially alter inactivation of LTB4 by the liver and may mediate neutrophil accumulation into the liver, thereby contributing to the pathogenesis of alcoholic hepatitis even when LTB4 biosynthesis occurs at some site distant to the liver.

摘要

低浓度乙醇会显著改变中性粒细胞趋化脂质白三烯B4（LTB4）的肝细胞代谢。LTB4的两种新代谢产物仅在有乙醇存在时才会出现，且保留了显著的生物活性。一种代谢产物3-羟基-LTB4在低至3×10⁻¹⁰ M的浓度下就能增加人中性粒细胞内的游离钙，在10 nM时还能诱导细胞形态改变并使其黏附于白蛋白包被的乳胶珠上。3-羟基-LTB4和3,20-二羟基-LTB4代谢产物也是有效的趋化激动剂，其半数有效浓度（ED50）分别为3.0 nM和9.0 nM。这些结果表明，乙醇的存在会极大地改变肝脏对LTB4的失活作用，并可能介导中性粒细胞在肝脏中的积聚，从而即使在LTB4生物合成发生在远离肝脏的某些部位时，也会促使酒精性肝炎的发病机制形成。