Antibody-independent activation of the classical pathway of human serum complement by lipid A is restricted to re-chemotype lipopolysaccharide and purified lipid A

Abstract

Incubation of most bacterial lipopolysaccharides (LPS) with normal human sera at 37C activates the serum complement system, resulting in decreased levels of hemolytic complement. A panel of R-chemotype LPS preparations isolated from Salmonella minnesota rough mutant strains, as well as smooth wild-type LPS from S. minnesota, Escherichia coli 055-B5, Serratia marcescens, and Yersinia enterolitica, were used to examine the effect of LPS polysaccharide chain length on LPS lipid (lipid A)-dependent activation of the classical pathway of complement (CPC). To examine specific lipid A-dependent activation of the CPC, sera deficient in alternative pathway of complement activity were prepared by the removal of factor D. Absorption of normal human sera with formalinized rabbit erythrocytes was found to remove natural antibodies, factors capable of forming LPS complexes which activate the CPC, or both. By using such factor D-depleted formalinized rabbit erythrocyteabsorbed normal human sera, only isolated lipid A and Re-chemotype LPS (R595 LPS) were found to activate the CPC. Thus, the presence of the additional monosaccharide L-glycero-D-mannoheptose in the Rd2 LPS oligosaccharide chain compared with the L-glycero-D-mannoheptose-deficient Re-chemotype LPS structure is sufficient to block lipid A-dependent activation of the CPC by LPS.

Legionella pneumophila lipopolysaccharide activates the classical complement pathway

“…The amount of fluid-phase L. pneumophila LPS required to activate complement in NHS is in agreement with the findings of several groups working with LPSs from other bacteria (6,13,32). Although we used LPS at concentrations of 1 mg/ml in most of the experiments described in this report, as little as 10 ,ug of LPS per ml was sufficient to activate the classical complement pathway.…”

“…These data suggested that the anti-LPS antibodies described here may be natural antibodies. We (24) and others (32) have noted that natural antibodies have low affinities and are difficult to remove by adsorption. Vukajlovich (32) reported that all NHS contains natural anti-rabbit E antibodies of the IgG and IgM classes that cross-react with antigenic determinants found on LPS polysaccharide.…”

“…We (24) and others (32) have noted that natural antibodies have low affinities and are difficult to remove by adsorption. Vukajlovich (32) reported that all NHS contains natural anti-rabbit E antibodies of the IgG and IgM classes that cross-react with antigenic determinants found on LPS polysaccharide. This conclusion was based on the observation that adsorption of NHS with rabbit E reduced the ability of LPS from Serratia marcescens, E. coli, and Y. enterocolitica to activate the classical complement pathway.…”

“…DISCUSSION effluent; 0, It is well established that LPS produced by enteric bacteria such as Salmonella spp. and Escherichia coli activate complement (16,32). The polysaccharide portion of LPS is thought to be responsible for alternative pathway activation ated for 1 h (16), whereas the lipid A portion can activate the classical ed as previ-pathway independent of antibody (17,32).…”

“…and Escherichia coli activate complement (16,32). The polysaccharide portion of LPS is thought to be responsible for alternative pathway activation ated for 1 h (16), whereas the lipid A portion can activate the classical ed as previ-pathway independent of antibody (17,32). The incubation of ing amounts enterobacterial LPS in NHS primarily results in activation of concomitant the alternative pathway because the sites on lipid A that iption of C4 interact with classical pathway components are normally not h 0.51 mg of exposed (32).…”