Endothelial Cells Produce a Lipoxygenase Derived Chemo-Repellent which Influences Platelet/Endothelial Cell Interactions – Effect of Aspirin and Salicylate^[*]

Summary

We performed experiments to determine whether endothelial cells synthesize phospholipid metabolites via the lipoxygenase pathway and whether these metabolites influence platelet/vessel wall interactions. Monolayers of cultured human endothelial cells were incubated with ¹⁴C-arachidonic acid and their cyclo-oxygenase and lipoxygenase metabolites were extracted and identified by radioimmunoassay, thin layer chromatography and high performance liquid chromatography. We found that in addition to the membrane-associated production of PGI₂, endothelial cells synthesized a cytosol-associated metabolite, LOX, which was presumably derived through the lipoxygenase pathway. Inhibition of LOX was associated with an increase in PGI₂ production and inhibition of PGI₂ with an increase in LOX production. Under either condition, platelet adhesion to cultured endothelial cells was significantly decreased. In contrast, when both PGI₂ and LOX production were inhibited, platelet adhesion to endothelial cells was enhanced. Furthermore, when LOX was bound to a thrombogenic surface, platelet adhesion was significantly decreased whereas when arachidonic acid or 12-HETE was bound to the surface, platelet adhesion was increased. We conclude that endothelial cells produce not only a cyclo-oxygenase metabolite, but also a lipoxygenase metabolite, both of which influence platelet/endothelial cell interactions.

Keywords

Endothelial cell - Lipoxygenase metabolite LOX - Platelet chemo-repellent factor

Presented, in part, in abstract form at the IXth International Congress Society on Thrombosis and Haemostasis in Stockholm, Sweden, July, 1983.

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