Two Mechanisms for the Activation of Serum Complement by Bacterial Lipopolysaccharides: A Role for Lipid A in Only One of Them

Abstract

Abstract Preparations of lipopolysaccharide (LPS) from different bacterial sources vary significantly in their relative content of lipid A (LA) and polysaccharide (PS). As a number of biologic properties of LPS have been attributed to the LA region of the molecule, and as isolated LA has been demonstrated to activate complement, the relationship between the LA content of LPS and its anticomplementary activity was examined. Activation was determined by a) reduction in hemolysis of sensitized erythrocytes, b) alteration of the electrophoretic mobility of C3 in normal (NHS) and C2-deficient (C2-def) human serum, and c) consumption of early complement components C1, C4, and C2. Two antigenically similar preparations of LPS from Escherichia coli 0111:B4, which vary significantly in their relative ratio of LA:PS (LPS-I, low LA:PS and LPS-II, high LA:PS) were used. In addition, LPS from E. coli 055:B5, which is structurally similar but antigenically unrelated to LPS-I; LPS from Salmonella minnesota R595, which contains only LA and a trisaccharide; and purified LA itself were also examined.