Human umbilical vein endothelial cells generate leukotriene C 4 via microsomal glutathione S ‐transferase type 2 and express the CysLT 1 receptor

Certain immunocompetent myeloid cells, such as eosinophils, basophils and mast cells, have a large capacity to synthesize the potent proinflammatory and spasmogenic mediator leukotriene (LT) C 4 via a specific microsomal glutathione S ‐transferase (MGST) termed LTC 4 synthase (LTC4S). Here, we report that MGST2, a distant homologue of LTC4S, is abundantly expressed in Human umbilical vein endothelial cells (HUVEC) and converts LTA 4 into a single product, LTC 4 . Thus, using Northern blot, RT‐PCR, Western blot, and enzyme activity assays, we show that MGST2 is the main, if not the only, enzyme that converts LTA 4 into LTC 4 in membrane preparations of HUVEC. In fact, we failed to detect any expression of LTC4S, MGST1 or MGST3 in these cells, indicating that MGST2 is a critical enzyme for transcellular LTC 4 biosynthesis in the vascular wall. Unlike LTC4S, MGST2 prefers the naturally occurring free acid of LTA 4 over the methyl ester as substrate and is also susceptible to product inhibition with an IC 50 of about 1 µ m for LTC 4 . Moreover, HUVEC were found to express the CysLT 1 receptor in line with a paracrine and autocrine role for cysteinyl‐leukotrienes in endothelial cell function.