Macrophage factor X activator formation: metabolic requirements for synthesis of components.
The in vitro production of factor VII-like material and of tissue factor activity by murine thioglycollate exudate macrophages was measured by amidolytic assays. Tissue factor activity was inducible by endotoxin, and its induction was inhibited by 1 microgram/mL of actinomycin D, 10 micrograms/mL of cycloheximide, and 0.2 micrograms/mL of tunicamycin. Soluble factor VII-like material was secreted by macrophages into culture supernatants. The amount produced was not influenced by further activation of the cells by endotoxin, nor was its production inhibited significantly by 1 microgram/mL actinomycin D or 0.2 micrograms/mL tunicamycin. The production of the factor VII-like material was inhibited by 10 micrograms/mL of cycloheximide, and its appearance in culture supernatants was enhanced significantly by the addition of vitamin K1. When lysates of activated macrophages were suspended in ultracentrifuged culture supernatants, a particulate factor X activator was formed. Centrifugation at 100,000 g pelleted the factor X activator and left no factor VII-like material in the supernatant. The data indicate that thioglycollate-induced exudate macrophages make and excrete factor VII-like material, and this production is not modulated by further activation. However, activation of the macrophages induces tissue factor production. The factor X activator appears to result from the interaction and complexing of the soluble factor VII-like material and the membrane-bound tissue factor.
D000818:Animals; D001780:Blood Coagulation Tests; D001921:Brain / Q000378:metabolism; D005167:Factor VII / Q000378:metabolism; D005170:Factor X / Q000096:biosynthesis* / Q000378:metabolism; D015951:Factor Xa; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D011498:Protein Precursors / Q000096:biosynthesis / Q000378:metabolism; D011817:Rabbits; D013925:Thromboplastin / Q000378:metabolism; D014812:Vitamin K / Q000494:pharmacology
D011498:Protein Precursors; D014812:Vitamin K; D005167:Factor VII; D005170:Factor X; D013925:Thromboplastin; D015951:Factor Xa