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

M R Buchanan; R W Butt; Z Magas; J Van Ryn; J Hirsh; D J Nazir

doi:10.1055/s-0038-1661303

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1985; 53(03): 306-311
DOI: 10.1055/s-0038-1661303

Original Article

Schattauer GmbH Stuttgart

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

Authors

M R Buchanan

The Departments of Pathology and Medicine, McMaster University, Hamilton, Ontario, Canada
R W Butt

The Departments of Pathology and Medicine, McMaster University, Hamilton, Ontario, Canada
Z Magas

The Departments of Pathology and Medicine, McMaster University, Hamilton, Ontario, Canada
J Van Ryn

The Departments of Pathology and Medicine, McMaster University, Hamilton, Ontario, Canada
J Hirsh

The Departments of Pathology and Medicine, McMaster University, Hamilton, Ontario, Canada
D J Nazir

The Departments of Pathology and Medicine, McMaster University, Hamilton, Ontario, Canada

Abstract

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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

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References

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

Authors

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