Pologe L G, Cramer E B, Pawlowski N A, Abraham E, Cohn Z A, Scott W A
J Exp Med. 1984 Oct 1;160(4):1043-53. doi: 10.1084/jem.160.4.1043.
Cultured endothelial cells from human umbilical cord labeled with [3H]20:4 release radiolabel when exposed to leukotrienes C or D (LTC or LTD). The major radiolabeled 20:4 metabolite recovered in the culture medium was prostacyclin. Both leukotrienes produced a dose-dependent synthesis of prostacyclin, with a maximal response at 10(-7) M leukotriene. LTC promoted a twofold greater response than did LTD at all concentrations tested (10(-9) to 10(-7) M). In contrast, no release of radiolabel above basal levels was evident with a challenge of LTE or LTB at the same concentrations. Endothelial cells metabolize approximately 40-50% of exogenously supplied LTC to LTD and LTE in 60 min. Levels of alpha-glutamyltranspeptidase (gamma-GTPase), the ectoenzyme reported to convert LTC or LTD, were detected in intact endothelial cells with the chromogenic substrate L-gamma-glutamyl-p-nitroanilide at levels sufficient to account for the observed rate of LTC metabolism. High concentrations of the gamma-GTPase inhibitors, glutathione and AT-125, blocked the metabolism of LTC by endothelium. These results suggest that degradation of leukotrienes by endothelium may be one mechanism for inactivation of these lipid mediators.
用[3H]20:4标记的人脐带培养内皮细胞在暴露于白三烯C或D（LTC或LTD）时会释放放射性标记物。在培养基中回收的主要放射性标记的20:4代谢物是前列环素。两种白三烯均产生剂量依赖性的前列环素合成，在10(-7)M白三烯时达到最大反应。在所有测试浓度（10(-9)至10(-7)M）下，LTC促进的反应比LTD大两倍。相比之下，在相同浓度下用LTE或LTB刺激时，未观察到高于基础水平的放射性标记物释放。内皮细胞在60分钟内将约40-50%的外源性供应的LTC代谢为LTD和LTE。用生色底物L-γ-谷氨酰-p-硝基苯胺在完整内皮细胞中检测到据报道可转化LTC或LTD的外切酶α-谷氨酰转肽酶（γ-GTPase）的水平，其水平足以解释观察到的LTC代谢速率。高浓度的γ-GTPase抑制剂谷胱甘肽和AT-125可阻断内皮细胞对LTC的代谢。这些结果表明内皮细胞对白三烯的降解可能是这些脂质介质失活的一种机制。
