Albumin redirects platelet eicosanoid metabolism toward 12(S)-hydroxyeicosatetraenoic acid.
Albumin is a major determinant of eicosanoid formation, affecting autacoids important in cell-cell interactions. We delineated three mechanisms by which albumin controlled platelet eicosanoid formation: 1) Albumin diverted free arachidonate toward 12-lipoxygenation. 2) Albumin enhanced release of arachidonate from phospholipids. 3) Albumin inhibited incorporation of arachidonate from the medium into platelet phospholipids. 12(S)-Hydroxyheptadecatrienoic acid (12-HHTrE) formation was reduced 70% by albumin as compared to that formed in albumin-free medium. In sharp contrast, formation of 12(S)-hydroxyeicosatetraenoic acid (12-HETE), the platelet lipoxygenase product, was much less influenced by albumin. Moreover, 12-HETE production in the presence of albumin was markedly increased and prolonged after aspirin treatment. These data suggested that albumin redirected released endogenous arachidonate from cyclooxygenase to lipoxygenase. Therefore, the metabolic fate of arachidonate present in the medium of stimulated platelets was studied by adding tracer [3H]arachidonate 30 sec before thrombin. Albumin increased arachidonate metabolism by lipoxygenase 7-fold as compared to albumin-free controls, while cyclooxygenation increased 2.7-fold. Redirection of eicosanoid metabolism by albumin toward lipoxygenase products constitutes a heretofore undescribed and potentially important physiological role for albumin. In vitro utilization of albumin may reflect in vivo events in thrombosis and hemostasis more accurately than previous studies without albumin could appreciate.
Broekman
M J
MJ
Department of Medicine, New York Veterans Administration Medical Center, NY 10010.
Eiroa
A M
AM
Marcus
A J
AJ
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D015777:Eicosanoids / Q000097:blood*; D005227:Fatty Acids / Q000032:analysis; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood*; D012709:Serum Albumin / Q000502:physiology*
D001095:Arachidonic Acids; D015777:Eicosanoids; D005227:Fatty Acids; D006893:Hydroxyeicosatetraenoic Acids; D012709:Serum Albumin; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001241:Aspirin