Evidence for different requirements in physical state for the interaction of lipopolysaccharides with the classical and alternative pathways of complement.
The influence of the state of aggregation of lipopolysaccharides upon their ability to interact with serum complement via either the classical or alternative pathway was studied. The anticomplement properties of two chromatographically distinct fractions of a phenol-extracted lipopolysaccharide isolated from Serratia marcescens were assessed by means of the standard sheep erythrocyte hemolytic assay and an alternative pathway-selective kinetic assay using rabbit erythrocytes. Both the high molecular weight PI fraction and the lower molecular weight PII fraction exerted anti-complement activity as determined in the sheep erythrocyte assay. Conversion of fractions PI and PII to their more soluble triethylamine salt forms resulted in a decrease in sedimentation coefficients and a corresponding loss of anticomplement activity. Further, the anticomplement activity of fractions PI and PII in the sheep erythrocyte assay was inhibited by polymyxin B, indicating a role for the lipid A region. Unlike the PII fraction, only the PI fraction can activate serum complement via the alternative pathway. This activity is not inhibited by polymyxin B, indicating that the response is not lipid A-mediated. Significantly, solubilization of the PI fraction with triethylamine had no effect on its ability to activate the alternative pathway. These studies clearly demonstrate that the interaction between lipopolysaccharides and serum complement is influenced by the state of lipopolysaccharide aggregation. However, this appears to be the case for lipopolysaccharide activation of the classical pathway but not of the alternative pathway.
D000328:Adult; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003167:Complement Activation / Q000187:drug effects*; D003169:Complement Inactivator Proteins; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D003171:Complement Pathway, Classical / Q000187:drug effects*; D004912:Erythrocytes / Q000276:immunology; D005021:Ethylamines / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010636:Phenols; D011112:Polymyxin B / Q000494:pharmacology; D011817:Rabbits; D012706:Serratia marcescens / Q000378:metabolism; D012756:Sheep
D003169:Complement Inactivator Proteins; D005021:Ethylamines; D008070:Lipopolysaccharides; D010636:Phenols; C012749:anticomplement; D011112:Polymyxin B; C016162:triethylamine