Biological activities of lipopolysaccharides are determined by the shape of their lipid A portion

摘要: Lipopolysaccharide (LPS) represents a major virulence factor of Gram-negative bacteria ('endotoxin') that can cause septic shock in mammals including man. The lipid anchor LPS to the outer membrane, A, has peculiar chemical structure, harbours 'endotoxic principle' and is responsible for expression pathophysiological effects. Chemically modified A be endotoxically inactive, but may express strong antagonistic activity against LPS, property utilized antisepsis treatment. We show here these different biological activities are directly correlated with molecular shape A. Only (hexaacyl) conical/concave shape, cross-section hydrophobic region being larger than hydrophilic region, exhibited interleukin-6 (IL-6)-inducing capacity. Most strikingly, correlation between cylindrical was established: IL-6 induction by enterobacterial inhibited cylindrically shaped except compounds reduced headgroup charge. action interpreted assuming molecules intercalate into cytoplasmic membrane mononuclear cells, subsequently blocking putative signaling protein shape.