The induction of a unique procoagulant activity in rabbit hepatic macrophages by bacterial lipopolysaccharides.
Disseminated intravascular coagulation (DIC) is a common occurrence during clinical sepsis and can be induced in the experimental host by LPS. Fibrin deposition in the hepatic microcirculation has been observed within 30 min of i.v. injection of LPS. Because mononuclear phagocytes have been shown to produce a PCA after exposure to LPS, we have examined the ability of a homogeneous population of explanted hepatic macrophages to express PCA. Addition of as little as 10 ng/ml of LPS stimulated a 15- to 20-fold increase in PCA over control culture levels within 7 1/2 hr post-treatment. The PCA was found to be membrane-associated, with approximately 90 to 95% of the total PCA present in the cellular lysates, and more than 85% was inhibited by pretreatment of the cells with the diazonium salt of sulfanilic acid, an inhibitor of ecto-enzymes. In contrast to tissue thromboplastin produced by other M phi populations, the H-M phi PCA was found to be markedly sensitive both to heat inactivation at 56 degrees C and to inhibition by 1 mM DFP. Additionally, assays involving both a 1-stage coagulation test as well as an enzyme assay with a Factor Xa-specific substrate (using normal and deficient human plasmas) demonstrated that the H-M phi PCA appears to activate Factor X directly. Unlike tissue thromboplastin, the H-M phi PCA is non-dependent of Factor VII activation. These studies: 1) demonstrate the LPS induces a unique PCA in the H-M phi, and 2) support a role for the H-M phi in the initiation of DIC in endotoxemic shock.
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D004926:Escherichia coli; D007531:Isoflurophate / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology*; D008264:Macrophages / Q000378:metabolism*; D011817:Rabbits; D012475:Salmonella; D013925:Thromboplastin / Q000378:metabolism
D008070:Lipopolysaccharides; D007531:Isoflurophate; D013925:Thromboplastin