Abstract
Previous studies have demonstrated that endotoxin administered in a single intravenous dose produced increased platelet and fibrinogen production. To determine if the lipid moiety of the endotoxin was implicated, we studied the effect of intact endotoxin (E. coli 026:B6), lipid A, lipid A incorporated into liposomes, and lipid A solubilized in triethylamine (TEA) on platelet and fibrinogen production in male New Zealand rabbits. Animals received these preparations by single intravenous 1 h infusions of 1.0, 5.0, 10.0, 25.0, or 50.0 μg/kg body weight. Selenomethionine-75Se was injected 18 h after infusion, and the percentages of incorporation into platelet and fibrinogen were used to measure thrombopoiesis and fibrinogen synthesis. All 4 types of infusions increased both platelet production and fibrinogen synthesis and a dose-response relationship was observed; however, the threshold dose for stimulation varied with the type of material infused. More lipid A (by weight) was required to stimulate either platelets or fibrinogen than any of the other materials infused. When incorporated into liposomes or solubilized with TEA, lipid A produced a response similar to that produced by intact endotoxin. These data suggest that the lipid A moiety itself can stimulate platelet and fibrinogen production.
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