Sala A, Folco G
Department of Pharmacological Sciences, Università degli Studi di Milano, Via Balzaretti 9, Milan, 20133, Italy.
Biochem Biophys Res Commun. 2001 May 25;283(5):1003-6. doi: 10.1006/bbrc.2001.4865.
Cysteinyl leukotrienes (cys-LT) have been historically involved with the pathogenesis of asthma, and cys-LT receptor antagonists and synthesis inhibitors are currently in use for the therapy of this disease. Nevertheless cys-LT possess very potent proinflammatory activities and may play a significant role in inflammatory processes other than asthma. Recent evidences obtained in our laboratory, as well as in others, show that unexpected, biologically significant amounts of cys-LT are formed upon cell-cell cooperation between neutrophils and endothelial cells, resulting from transfer of the synthesis intermediate leukotriene A4 from neutrophils to endothelial cells. Cys-LT formed upon neutrophil adhesion to endothelial cells may contribute to the alterations of microvasculature associated with the inflammatory response. In particular, nonsteroidal anti-inflammatory drug (NSAIDs)-induced neutrophil adhesion to gastric wall microvessels may contribute to the gastric damage associated to the use of NSAIDs. In agreement with this hypothesis, dual 5-LOX/COX inhibitors are characterized by reduced gastric damage when compared to nonspecific COX-inhibitors. Evidence provide support for the involvement of cys-LT in neutrophil-dependent inflammatory responses and suggest new potential application of 5-LO inhibition in anti-inflammatory pharmacological treatment.
半胱氨酰白三烯(cys-LT)一直以来都与哮喘的发病机制有关,目前半胱氨酰白三烯受体拮抗剂和合成抑制剂被用于治疗这种疾病。然而,半胱氨酰白三烯具有非常强大的促炎活性,可能在哮喘以外的炎症过程中发挥重要作用。我们实验室以及其他实验室最近获得的证据表明,中性粒细胞与内皮细胞之间的细胞间合作会产生意想不到的、具有生物学意义的大量半胱氨酰白三烯,这是由于合成中间体白三烯A4从中性粒细胞转移到内皮细胞所致。中性粒细胞黏附于内皮细胞时形成的半胱氨酰白三烯可能导致与炎症反应相关的微血管改变。特别是,非甾体抗炎药(NSAIDs)诱导的中性粒细胞黏附于胃壁微血管可能导致与使用NSAIDs相关的胃损伤。与这一假设一致,与非特异性COX抑制剂相比,双重5-脂氧合酶/COX抑制剂的特点是胃损伤减少。证据支持半胱氨酰白三烯参与中性粒细胞依赖性炎症反应,并提示5-脂氧合酶抑制在抗炎药物治疗中的新潜在应用。