The endotoxin-induced procoagulant of mouse exudate macrophages: a factor-X activator.
The properties of mouse macrophage procoagulant induced by endotoxin in vitro were studied by the acceleration of clotting and by chromogenic assays using as substrates human plasma and bovine components, which are not activated by mouse tissue factor. Maximal macrophage procoagulant activity occurred when activated cells were lysed in culture supernatant fluids, suggesting the interaction of cellular and supernatant factors. This procoagulant was clearly able to activate bovine factor X. The procoagulant also appeared to have prothrombinase activity. However, additional experiments suggested that the bulk of this activity was due to the activation of factor X contaminating the prothrombin. The production of the procoagulant was inhibited by warfarin (5 microM). Its activity was inhibited by 1 mM diisopropylfluorophosphate and unaffected by iodoacetamide, indicating that the procoagulant is a serine protease. Macrophage culture supernatants contained factor-VII-like activity. Neither mouse tissue factor nor macrophage culture supernatants alone activated bovine factor X. The two combined served as an efficient factor-X activator. Active supernatant factor (factor-VII-like) was not produced by macrophages cultured in the presence of warfarin, while the production of the macrophage cellular factor was unaffected by the presence of warfarin. I conclude that exudate macrophages cultured in vitro make and secrete factor VII or a factor-VII-like substance into the culture supernatant. When activated macrophages are lysed in this supernatant, the interaction of a cellular factor (? tissue factor) and factor VII gives rise to a factor-X activator.
D000818:Animals; D003029:Coagulants / Q000032:analysis* / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D005165:Factor V / Q000494:pharmacology; D005170:Factor X / Q000378:metabolism* / Q000494:pharmacology; D015951:Factor Xa; D005260:Female; D006629:Hirudins / Q000494:pharmacology; D007531:Isoflurophate / Q000494:pharmacology; D008264:Macrophages / Q000032:analysis* / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D013045:Species Specificity; D014361:Trypsin Inhibitors / Q000494:pharmacology; D014812:Vitamin K / Q000494:pharmacology; D014859:Warfarin / Q000494:pharmacology
D003029:Coagulants; D004731:Endotoxins; D006629:Hirudins; D014361:Trypsin Inhibitors; C022475:prothrombinase complex; D014812:Vitamin K; D007531:Isoflurophate; D014859:Warfarin; D005165:Factor V; D005170:Factor X; D015951:Factor Xa