Antibody-independent activation of the classical pathway of human serum complement by lipid A is restricted to re-chemotype lipopolysaccharide and purified lipid A.
Incubation of most bacterial lipopolysaccharides (LPS) with normal human sera at 37 degrees C 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 O55-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 erythrocyte-absorbed 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.
D003167:Complement Activation / Q000187:drug effects*; D003172:Complement C1 / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000187:drug effects*; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008050:Lipid A / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*
D003172:Complement C1; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008050:Lipid A; D008070:Lipopolysaccharides