Endothelium and underlying membrane reactivity with platelets, leukocytes and tumor cells: regulation by the lipoxygenase-derived fatty acid metabolites, 13-HODE and HETES.

We hypothesize that the ratio of intracellular 13-hydroxy-octadeca-dienoic acid (13 HODE) and hydroxy-eicosatetraenoic acid (5-, 12- and/or 15-HETE) influences the expression or presentation of adhesive moieties on platelets, leukocytes, malignant cells and endothelial cells, thereby influencing their subsequent adhesive interactions. Thus, we demonstrate that under unstimulated conditions, these cells preferentially synthesize linoleic acid via their lipoxygenase enzymes into 13-HODE, the intracellular level of which is associated with limited or no cell adhesion, while following stimulation, the same cells preferentially metabolize arachidonic acid via the lipoxygenase enzyme into HETEs, the production of which is associated with enhanced adhesion. Which metabolite is synthesized by these cells and the subsequent adhesivity of these cells appear to be dependent upon both the intracellular level of cAMP and the ratio of linoleic and arachidonic acid substrates. This suggests that manipulation of this ratio will have significant effects on the adhesive events involved in the pathogenesis of thrombosis, inflammation and metastasis.