Structural features of Salmonella typhimurium lipopolysaccharide required for activation of tissue factor in human mononuclear cells

Abstract

Activation of mononuclear cell tissue factor was examined utilizing lipopolysaccharides obtained from wild-type and both R(c) and R(e) mutants of S. typhimurium. Wild-type (smooth) lipopolysaccharide, galactose-deficient (R(c)) lipopolysaccharide, heptose-deficient (R(e)) lipopolysaccharide, and lipid A preparations were all active in their ability to generate tissue factor activity in human mononuclear cells grown in tissue culture. Polymyxin B has been reported to prevent some of the lethal effects of endotoxin in vivo, and the drug reportedly binds to the 2-keto-3-deoxyoctulosonate-lipid A region of the lipopolysaccharide molecule. Polymyxin B was effective in inhibiting the tissue factor generating activity of wild-type lipopolysaccharide, R(e) lipopolysaccharide, and lipid A in a dose-dependent fashion. Treatment of lipid A preparations with mild alkali abolished the ability of these preparations to activate tissue factor in cells. Analogous to many of the other biologic properties of lipopolysaccharide, tissue factor activation in human mononuclear cells appears to depend upon the integrity of the lipid A portion of the molecule.