Conrad D J
Department of Medicine, San Diego Veterans Administration Medical Center, University of California, CA, USA.
Clin Rev Allergy Immunol. 1999 Spring-Summer;17(1-2):71-89. doi: 10.1007/BF02737598.
12/15-Lipoxygenase is a highly regulated lipid-peroxidating enzyme whose expression and arachidonic acid metabolites are implicated in several important inflammatory conditions including airway and glomerular inflammation as well as atherosclerosis. Tissue expression of the original 12/15-lipoxygenase is well characterized in reticulocytes, eosinophils, airway epithelial cells, and monocytes/macrophages and is likely in other cell systems and tissues under specific conditions. The physiologic role of this family of enzymes is dependent on the context in which it is expressed. In general, the arachidonic acid metabolites antagonize inflammatory responses and counteract the proinflammatory effects of the 5-lipoxygenase pathway. However, certain diHETEs are associaled with pro-inflammatory effects, specifically neutrophilic and eosiniphilic chemotaxis. The direct action of these enzymes on complex lipids and cellular membranes also links them to such significant process as reticulocyte maturation, LDL oxidation in atherosclerosis and pulmonary host defenses. The availability of new specific inhibitors and murine lines that lack expression of the homologous 12-lipoxygenase will allow confirmation of many of these effects with in vivo models of inflammation.
12/15-脂氧合酶是一种受到高度调控的脂质过氧化酶，其表达及花生四烯酸代谢产物与多种重要的炎症状态有关，包括气道和肾小球炎症以及动脉粥样硬化。原始12/15-脂氧合酶的组织表达在网织红细胞、嗜酸性粒细胞、气道上皮细胞以及单核细胞/巨噬细胞中已有充分描述，在特定条件下其他细胞系统和组织中可能也有表达。该酶家族的生理作用取决于其表达的环境。一般来说，花生四烯酸代谢产物拮抗炎症反应并抵消5-脂氧合酶途径的促炎作用。然而，某些二羟二十碳四烯酸（diHETEs）与促炎作用相关，特别是嗜中性粒细胞和嗜酸性粒细胞趋化作用。这些酶对复合脂质和细胞膜的直接作用也将它们与网织红细胞成熟、动脉粥样硬化中的低密度脂蛋白氧化以及肺部宿主防御等重要过程联系起来。新型特异性抑制剂和缺乏同源12-脂氧合酶表达的小鼠品系的可得性，将有助于利用体内炎症模型证实其中许多作用。
