Gormand F, Chabannes B, Moliere P, Perrin-Fayolle M, Lagarde M, Pacheco Y
Laboratoire d'Immunoallergologie Respiratoire and Unite Inserm 352, Centre Hospitalier Lyon-Sud, France.
Prostaglandins. 1996 Apr;51(4):263-73. doi: 10.1016/0090-6980(96)00021-4.
12-HETE, the major lipoxygenase end-product of platelets and macrophages, may be released in contact of bronchial epithelium in inflammatory diseases of the lung. We have studied the outcome of 12-HETE in presence of human bronchial epithelial cells (HBEC). When HBEC were incubated with [3H]12-HETE for 30 minutes, 27.5% of total radioactivity was found in HBEC and 72.5% in supernatants. Unesterified 12-HETE accounted for 22.4% of total radioactivity, 4.5% being recovered in phospholipids, preferentially in phosphatidylcholine and phosphatidylethanolamine. No incorporation in neutral lipids was detected. 72.9% of the incubated radioactivity was recovered in un identified metabolites. As 12-HETE has been shown to modulate the expression and production of various proteins, the consequence of the 12-HETE uptake on the release of GM-CSF and IL8 by HBEC was assessed. HBEC from control subjects were cultured for 24 hours with 12-HETE (10(-9) to 10(-7)M) in the presence or absence of TNF alpha. Detectable amounts of both cytokines were released in the supernatant in basal conditions at 24hr, and TNF alpha increased significantly the release of GM-CSF. 12-HETE at 10(-7)M weakly but significantly decreased the TNF-induced release of GM-CSF from HBEC. Thus the uptake of 12-HETE could affect the epithelial cell function in some situations.
12-羟基二十碳四烯酸（12-HETE）是血小板和巨噬细胞主要的脂氧合酶终产物，在肺部炎症性疾病中，它可能在与支气管上皮接触时释放出来。我们研究了12-HETE在人支气管上皮细胞（HBEC）存在时的情况。当将HBEC与[3H]12-HETE孵育30分钟时，发现HBEC中占总放射性的27.5%，上清液中占72.5%。未酯化的12-HETE占总放射性的22.4%，4.5%在磷脂中回收，优先存在于磷脂酰胆碱和磷脂酰乙醇胺中。未检测到其掺入中性脂质。72.9%的孵育放射性在未鉴定的代谢产物中回收。由于已证明12-HETE可调节多种蛋白质的表达和产生，因此评估了12-HETE摄取对HBEC释放粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素8（IL8）的影响。来自对照受试者的HBEC在有或无肿瘤坏死因子α（TNFα）的情况下，用12-HETE（10^(-9)至10^(-7)M）培养24小时。在基础条件下，24小时时上清液中可检测到两种细胞因子的释放量，并且TNFα显著增加了GM-CSF的释放。10^(-7)M的12-HETE虽微弱但显著降低了TNF诱导的HBEC释放GM-CSF。因此，在某些情况下，12-HETE的摄取可能会影响上皮细胞功能。
