Incorporation of platelet and leukocyte lipoxygenase metabolites by
cultured vascular cells
AI Schafer, H Takayama, S Farrell and MA Gimbrone
When arachidonic acid metabolism is studied during platelet-endothelial
interactions in vitro, the predominant cyclooxygenase end products of each
cell type (thromboxane B2 and 6-keto-prostaglandin-F1 alpha, respectively)
are essentially completely recovered in the cell-free supernatants of these
reactions. In contrast, 50% of 12-hydroxy- 5,8,10,14-eicosatetraenoic acid
(12-HETE), the major lipoxygenase metabolite from platelets, is released
into the cell-free supernatant. In investigating the basis of this
observation, we have found that platelet lipoxygenase metabolites were
generated to the same extent during these coincubations but became rapidly
incorporated into the endothelial cells. The endothelial cell-associated
12-HETE was present not only as free fatty acid, but was also incorporated
into cellular phospholipids and triglycerides. When purified 3H-12-HETE,
3H-5-HETE (the major hydroxy acid lipoxygenase product of leukocytes), and
3H- arachidonic acid (the common precursor of these metabolites) were
individually incubated with suspensions of cultured bovine aortic
endothelial cells or smooth muscle cells, different patterns of
intracellular lipid distribution were found. In endothelial cells, 12- HETE
was incorporated equally into phospholipids and triglycerides, whereas
5-HETE was incorporated preferentially into triglycerides, and arachidonic
acid was incorporated into phospholipids. In smooth muscle cells, both
12-HETE and 5-HETE showed more extensive incorporation into triglycerides.
The rapid and characteristic incorporation and esterification of platelet
and leukocyte monohydroxy fatty acid lipoxygenase products by endothelial
and smooth muscle cells suggests a possible physiologic role for these
processes in regulating vascular function.
Volume 67,
Issue 2,
pp. 373-378,
02/01/1986
Copyright © 1986 by The American Society of Hematology
