Endotoxin induced disseminated intravascular clotting: evidence that it is mediated by neutrophil production of tissue factor
Lerner, R.G.; Goldstein, R.; Cummings, G.
Thrombosis Research 11(2): 253-261
1977
ISSN/ISBN: 0049-3848 PMID: 905976 Document Number: 118761
Cycloheximide is a potent inhibitor of protein synthesis. Its effects on endotoxin induced human neutrophil tissue factor production in vitro and endotoxin induced disseminated intravascular clotting (DIC) in rabbits were examined. Endotoxin [from Escherichia coli] added to citrated whole human blood led to the production of tissue factor except when neutrophils were absent from the blood. The production of this tissue factor was inhibited by cyclohexmide. Cycloheximide added after the tissue factor was formed had no effect. Neutrophil production of tissue factor apparently depends on protein synthesis. Eight steroid prepared rabbits were given i.v. cycloheximide prior to and after endotoxin injection. None of the rabbits developed DIC as measured by change in fibrinogen level or development of glomerular capillary thrombi. Six rabbits given endotoxin alone showed a 37% mean drop in fibrinogen level and 4 showed glomerular capillary thrombi. Rabbits treated with cycloheximide alone did not show any glomerular fibrin or change in fibrinogen level. They were capable of developing DIC since infusion of endotoxin and rabbit brain tissue factor caused a fall in fibriongen level and development of glomerular fibrin. This adds further evidence that neutrophil production of tissue factor is necessary for endotoxin induced DIC.