Host resistance to lipopolysaccharides in the pathogenesis of multiple sclerosis and membranoproliferative glomerulonephritis.
Host resistance against bacterial lipopolysaccharides (L.P.S.) and especially against its toxic part lipid A has earlier been demonstrated in biological assays. In this paper an aryl-esterase is shown to be associated with alfa-1-lipoprotein (ArE) and is probably responsible for the detoxification of L.P.S. in man. Furthermore C3 is shown to be activitated by L.P.S. From these facts it is suggested that ArE performs the initial degradation of L.P.S. followed by complement activation and trapping of the L.P.S.--complement complex in the reticuloendothelial system. It is postulated that a deficient host response against L.P.S. can be the triggering mechanism in multiple sclerosis due to the lack of ArE in myelin, and that an infectious-agent/L.P.S. syndrome can activate latent infections in connection with a severe hyperreactivity to L.P.S. Preliminary investigations in patients with membranoproliferative glomerulonephritis have shown low levels of ArE in serum. This change, together with the low C3 values in these patients, may result in deficient L.P.S. detoxification and it is suggested that L.P.S. are at least partly responsible for the production of C3 nephritic factor.
D000936:Antigen-Antibody Complex; D001921:Brain / Q000201:enzymology / Q000276:immunology; D002265:Carboxylic Ester Hydrolases / Q000172:deficiency; D003176:Complement C3 / Q000172:deficiency; D003178:Complement C3 Nephritic Factor / Q000096:biosynthesis; D004926:Escherichia coli / Q000276:immunology; D005921:Glomerulonephritis / Q000209:etiology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications*; D007678:Kidney Glomerulus / Q000201:enzymology / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D009103:Multiple Sclerosis / Q000209:etiology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*
D000936:Antigen-Antibody Complex; D003176:Complement C3; D003178:Complement C3 Nephritic Factor; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; D002265:Carboxylic Ester Hydrolases