Membrane receptors on rat hepatocytes for the inner core region of bacterial lipopolysaccharides.
Bacterial lipopolysaccharides (LPS) are potent endotoxins that are thought to be involved in the pathogenesis of Gram-negative septicemia. The liver is known to be the primary organ responsible for the clearance of LPS from the systemic circulation in mammals. In this work, 125I-labeled LPS have been used in a filtration assay for the specific binding of LPS to intact rat hepatocytes. Eight S-form (smooth) LPS with complete O-specific polysaccharide chains isolated from different O-serotypes of Salmonella and Escherichia coli as well as nine R-form (rough) LPS isolated from Salmonella mutants deficient in synthesis of their core oligosaccharides were used in this study. All 125I-labeled S-form LPS and R-form LPS, except Re, show specific binding to isolated hepatocytes. The binding is saturable, is inhibited with excess unlabeled homologous or heterologous LPS but not lipid A, and is trypsin sensitive. L-Glycero-D-mannoheptose (heptose), a constituent of the inner core region of almost all LPS, is a potent inhibitor of the specific binding of 125I-labeled Rb2 LPS, whereas other monosaccharides, including 3-deoxy-D-manno-2-octulosonic acid (KDO), have weak or negligible inhibitor activity. These results strongly suggest the presence of a lectin-like receptor for the LPS inner core region (heptose-KDO region) on the plasma membrane of rat hepatocytes.
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Casualty Care Research Department, Naval Medical Research Institute, Bethesda, Maryland 20814-5055.
D000818:Animals; D001667:Binding, Competitive; D002241:Carbohydrates / Q000494:pharmacology; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D002850:Chromatography, Gel; D004926:Escherichia coli / Q000276:immunology; D007700:Kinetics; D008050:Lipid A / Q000378:metabolism; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000378:metabolism*; D008099:Liver / Q000276:immunology*; D008358:Mannose / Q000494:pharmacology; D051381:Rats; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D012475:Salmonella / Q000276:immunology; D014357:Trypsin
D002241:Carbohydrates; D008050:Lipid A; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D014357:Trypsin; D008358:Mannose