MACROPHAGE FACTOR-X ACTIVATOR FORMATION - METABOLIC REQUIREMENTS FOR SYNTHESIS OF COMPONENTS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 65  (1) , 169-175
Abstract
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 .mu.g/ml of actinomycin D, 10 .mu.g/ml of cycloheximide, and 0.2 .mu.g/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 .mu.g/ml actinomycin D or 0.2 .mu.g/ml tunicamycin. The production of the factor VII-like material was inhibited by 10 .mu.g/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. Thioglycollate-induced exudate macrophages apparently make and excrete factor VII-like material, and this production is not modulated by further activation. 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.