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/10⁵ 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.