Lipopolysaccharide structure influences the macrophage response via CD14-independent and CD14-dependent pathways

CD14, a protein expressed on the surface of monocytes and neutrophils, is a major receptor for lipopolysaccharide (LPS). Studies with normal and CD14- deficient macrophages show that responses to low concentrations of LPS requ ire expression of CD14, whereas responses to high concentrations of LPS are CD14-independent. Since LPS isolated from different bacterial species show s structural variability, studies were performed to determine whether diffe rences in LPS structure influence CD14-dependent and CD14-independent respo nses. Studies with LPS purified from Escherichia coil, Salmonella abortus s ubspecies equi, Salmonella minnesota, Pseudomonas aeruginosa, Neisseria men ingitidis, Bacteroides fragilis, and Rhodobacter sphaeroides show that the strongest CD14-dependent responses require a typical O-antigen, long carboh ydrate chains, at least 6 acyl chains in their lipid A, and 2-phosphorylate d Kdo moieties; wild-type LPS lacking a typical O-antigen and containing sh ort carbohydrate chains and 2-phosphorylated Kdo moieties induces the stron gest CD14-independent response.