Crooks S W, Stockley R A
Department of Medicine, Queen Elizabeth Hospital, Edgbastón, Birmingham, UK.
Int J Biochem Cell Biol. 1998 Feb;30(2):173-8. doi: 10.1016/s1357-2725(97)00123-4.
Leukotriene B4 is a pro-inflammatory mediator synthesised in myeloid cells from arachidonic acid. Synthesis is catalysed by 5-lipoxygenase and leukotriene A4 hydrolase and is increased by inflammatory mediators including endotoxin, complement fragments, tumor necrosis factor and interleukins. A nuclear membrane protein, 5-lipoxygenase activating protein, is an essential co-factor for 5-lipoxygenase. Leukotriene B4 induces recruitment and activation of neutrophils, monocytes and eosinophils. It also stimulates the production of a number of proinflammatory cytokines and mediators indicating an ability to augment and prolong tissue inflammation. Elevated levels of leukotriene B4 have been found in a number of inflammatory diseases and levels are related to disease activity in some of these. Initial data from pharmacological inhibition studies support a role for leukotriene B4 in the pathogenesis of neutrophil mediated tissue damage, and treatments which reduce its production or block its effects may prove beneficial in neutrophil mediated inflammatory diseases.
白三烯B4是一种在髓样细胞中由花生四烯酸合成的促炎介质。其合成由5-脂氧合酶和白三烯A4水解酶催化,并且会因包括内毒素、补体片段、肿瘤坏死因子和白细胞介素在内的炎症介质而增加。一种核膜蛋白,即5-脂氧合酶激活蛋白,是5-脂氧合酶的必需辅助因子。白三烯B4可诱导中性粒细胞、单核细胞和嗜酸性粒细胞的募集和活化。它还刺激多种促炎细胞因子和介质的产生,表明其具有增强和延长组织炎症的能力。在多种炎症性疾病中已发现白三烯B4水平升高,并且在其中一些疾病中其水平与疾病活动相关。药理学抑制研究的初步数据支持白三烯B4在中性粒细胞介导的组织损伤发病机制中的作用,减少其产生或阻断其作用的治疗方法可能对中性粒细胞介导的炎症性疾病有益。