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.
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October 01 1984
Stimulation of human endothelial cell prostacyclin synthesis by select leukotrienes.
L G Pologe
E B Cramer
N A Pawlowski
E Abraham
Z A Cohn
W A Scott
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1984) 160 (4): 1043–1053.
Citation
L G Pologe, E B Cramer, N A Pawlowski, E Abraham, Z A Cohn, W A Scott; Stimulation of human endothelial cell prostacyclin synthesis by select leukotrienes.. J Exp Med 1 October 1984; 160 (4): 1043–1053. doi: https://doi.org/10.1084/jem.160.4.1043
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