Some studies report that endothelial cells preferentially take up the
lipoxygenase-derived
arachidonic acid metabolite,
5-hydroxyeicosatetraenoic acid (5-HETE), released from stimulated leukocytes (polymorphonuclear leukocytes, PMNs), whereas others report that endothelial cells preferentially take up
12-HETE released from platelets. The
biological relevance of these observations, however, is unknown. Recently, we and others have found that, under basal conditions, endothelial cells, PMNs and
tumor cells metabolize
linoleic acid via the
lipoxygenase enzyme to
13-hydroxyoctadecadienoic acid (13-HODE). We propose that endogenous levels of these metabolites regulate blood-vessel wall cell adhesion. In this study, we have measured (1) the relative binding of 5-, 12- and
15-HETE, and
13-HODE to endothelial cell monolayers, and (2) their effects on endothelial cell adhesivity with platelets, PMNs and
tumor cells. There was a dose-related and specific binding of 5-[3H]
HETE to endothelial cells but no binding of 12- or
15-HETE or
13-HODE. Platelet or PMN adhesion to endothelial cells was unaffected by the
5-HETE binding, but
tumor cell adhesion was blocked by 40% (P less than 0.01). Interestingly, preincubation of endothelial cells with
13-HODE,
12-HETE or
15-HETE decreased platelet adhesion to endothelial cells (P less than 0.05), even though these metabolites did not bind to the endothelial cells. We conclude that
5-HETE preferentially binds to endothelial cells and interferes with a specific receptor for
tumor cells, whereas the other metabolites neither bind to cells nor affect cell adhesion.