Incubation of human endothelial cells with leukotriene A₄ resulted in the formation of leukotrienes B₄, C₄, D₄ and E₄. Endothelial cells did not produce leukotrienes after stimulation with the ionophore A23187 and/or exogenously added arachidonic acid. However, incubation of polymorphonuclear leukocytes with ionophore A23187 together with endothelial cells led to an increased synthesis of cysteinyl‐containing leukotrienes (364%, mean, n= 11) and leukotriene B₄ (52%) as compared to leukocytes alone. Thus, the major part of leukotriene C₄ recovered in mixed cultures was attributable to the presence of endothelial cells. Similar incubations of leukocytes with fibroblasts or smooth muscle cells did not cause an increased formation of leukotriene C₄ or leukotriene B₄.

The increased biosynthesis of cysteinyl‐containing leukotrienes and leukotriene B₄ in coincubations of leukocytes and endothelial cells appeared to be caused by two independent mechanisms. First, cell interactions resulted in an increased production of the total amount of leukotrienes, suggesting a stimulation of the leukocyte 5‐lipoxygenase pathway, induced by a factor contributed by endothelial cells.

Secondly, when endothelial cells prelabeled with [³⁵S]cysteine were incubated with either polymorphonuclear leukocytes and A23187, or synthetic leukotriene A₄, the specific activity of the isolated cysteinyl‐containing leukotrienes were similar. Thus, transfer of leukotriene A₄ from stimulated leukocytes to endothelial cells appeared to be an important mechanism causing an increased formation of cysteinyl‐containing leukotrienes in mixed cultures of leukocytes and endothelial cells.

In conclusion, the present study indicates that the vascular endothelium, when interacting with activated leukocytes, modulates both the quantity and profile of liberated leukotrienes.