Arachidonic acid metabolites produced by platelet-depleted human blood monocytes: a possible role in thrombogenesis.
The arachidonic acid metabolites produced by human peripheral blood monocytes were studied to determine which metabolites could have a role in thrombogenesis. Monocytes were found to be free of platelets by scanning electron microscopy and by measurement of 12-HETE. Human peripheral blood monocytes produce thromboxane as their major metabolite. Thromboxane levels reached a plateau at 12-16 hours of culture. Monocytes produced relatively little prostaglandin E2 or F2. In contrast to our control platelet preparation, neither A23187 (1-10 microM) nor exogenous arachidonic acid (0-40 microM) caused an increase in monocyte thromboxane B2. On the other hand, lipopolysaccharide (20 micrograms per ml), collagen (2.5 mg per 10(7) cells), and thrombin (5-10 units per ml) caused a two- to fivefold increase in monocyte thromboxane B2 in most donors but had no effect on prostaglandin F1 alpha levels. Blockage of thromboxane synthase by 1-benzylimidazole abolished thromboxane B2 production but did not increase prostaglandin F1 alpha. Finally, aspirin-treated platelets from a volunteer donor, which were refractory to 30 microM arachidonate, could be aggregated by isolated blood monocytes. Our data indicate that monocytes are capable of producing thromboxane in large amounts. The regulation of this increase, however, appears to be quite different from platelets. We postulate that monocytes may have a role in hemostasis by virtue of their ability to adhere at sites of vascular injury and release thromboxane, which may enhance platelet aggregation and thrombus formation.
Jones
C M
CM
Hematology Division, University of Texas Medical School and M.D. Anderson Hospital and Tumor Institute, Houston 77030.
Hall
E R
ER
Hester
J P
JP
Wu
K K
KK
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D001095:Arachidonic Acids / Q000378:metabolism*; D001790:Blood Physiological Phenomena; D001792:Blood Platelets; D002469:Cell Separation; D002478:Cells, Cultured; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007093:Imidazoles / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D010974:Platelet Aggregation; D013268:Stimulation, Chemical; D013927:Thrombosis / Q000209:etiology*; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000378:metabolism; D013997:Time Factors
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D007093:Imidazoles; C017062:1-benzylimidazole; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid