Yoshino H, Kitayama S, Morita K, Uchiyama Y, Shibata K, Shirakawa M, Okamoto H, Tsujimoto A, Dohi T
Department of Periodontics, Hiroshima University School of Dentistry, Japan.
J Lipid Mediat Cell Signal. 1994 May;9(3):225-34.
12-Hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) has been reported to be a chemoattractant for human neutrophils. To assess its cellular mechanism, we focused on the effect of 12-HETE on cytosolic Ca2+ ([Ca2+]i) and characterized the effect of 12-HETE on [Ca2+]i in human neutrophils. 12(S)- and 12(R)-HETE increased [Ca2+]i in the presence and absence of extracellular Ca2+ in a concentration-related fashion. The elevation of [Ca2+]i by 12(R)-HETE was completely abolished by pertussis toxin treatment. U-73122, a selective phospholipase C inhibitor, depressed the 12(S)- and 12(R)-HETE-induced rise in [Ca2+]i in the presence and absence of extracellular Ca2+. 12(R)-HETE resulted in the rapid production of inositol 1,4,5-trisphosphate (IP3). Furthermore, 12(R)-HETE elicited slight depolarization of neutrophils as assessed using the fluorescent dye bis-oxonol. These results provide evidence demonstrating the signal transduction pathway in human neutrophils after stimulation with 12-HETE and suggest that 12-HETE causes a rapid rise of [Ca2+]i by mobilizing Ca2+ from an IP3-sensitive intracellular Ca2+ pool in human neutrophils.
据报道，12-羟基-5,8,10,14-二十碳四烯酸（12-HETE）是人类中性粒细胞的一种趋化因子。为评估其细胞机制，我们重点研究了12-HETE对胞质Ca2+（[Ca2+]i）的影响，并对12-HETE对人类中性粒细胞[Ca2+]i的影响进行了表征。12(S)-HETE和12(R)-HETE在有或无细胞外Ca2+存在的情况下，均以浓度相关的方式增加[Ca2+]i。百日咳毒素处理可完全消除12(R)-HETE引起的[Ca2+]i升高。选择性磷脂酶C抑制剂U-73122在有或无细胞外Ca2+存在的情况下，均可抑制12(S)-HETE和12(R)-HETE诱导的[Ca2+]i升高。12(R)-HETE导致肌醇1,4,5-三磷酸（IP3）快速产生。此外，使用荧光染料双苯甲酰羟肟酸评估发现，12(R)-HETE可引起中性粒细胞轻微去极化。这些结果提供了证据，证明了12-HETE刺激后人类中性粒细胞中的信号转导途径，并表明12-HETE通过从人类中性粒细胞中对IP3敏感的细胞内Ca2+池中动员Ca2+，导致[Ca2+]i快速升高。
