Leukotriene induction of TxB2 in cultured bovine aortic endothelial cells

The leukotrienes (LT) are potent mediators of inflammation, capable of inducing plasma leakage from postcapillary venules and vasoconstriction of terminal arterioles. Some microvascular effects may be attributable to LT stimulation of thromboxane (Tx) synthesis. Incubation of primary cultures of bovine aortic endothelial cells with buffer, LTB4 (10(-8) M) or LTD4 (10(-8)M), resulted in TxA2 production in pg/10(5) cells to the extent of: 67 +/- 20, 571 +/- 180, and 333 +/- 60 respectively, as measured by radioimmunoassay of the stable metabolite TxB2. Endothelial pretreatment with the LTD4 receptor antagonist FPL55712 (10(-5)M) significantly blocked any LTB4- or LTD4-stimulated TxA2 synthesis. Pretreatment with the TxA2 synthetase inhibitor ketoconazole (10(-6)M) also prevented LTB4 of LTD4 stimulation of TxA2. Preincubation with DMTU (10(-5)M), an hydroxyl radical scavenger, decreased LTB4-induced release of TxA2 (405 +/- 40 and 366 +/- 20, respectively). These findings suggest that LT may mediate their inflammatory actions in vascular beds by stimulation of Tx release from endothelial cells.