title: Mycobacterium tuberculosis lipoarabinomannan enhances LPS-induced TNF-α production and inhibits NO secretion by engaging scavenger receptors.
abstract: Lipoarabinomannan capped with terminal oligomannosides (ManLAM) is a component of mycobacteria cell wall enabling Mycobacterium tuberculosis to infect macrophages. We found that short treatment (3.5h) of macrophage-like J774 cells and thioglycollate-elicited peritoneal murine macrophages with ManLAM and its deacylated form enhanced LPS-stimulated release of tumor necrosis factor-α (TNF-α). In contrast, prolong incubation of J774 cells with ManLAM (16h) led to inhibition of LPS-stimulated TNF-α production. LPS-triggered secretion of nitric oxide (NO) was suppressed by ManLAM and its deacylated form. Effects of ManLAM and its deacylated derivative were mimicked by dextran sulfate, a general ligand of scavenger receptors. The enhancement of LPS-induced TNF-α production by dextran sulfate was partially reversed by an antibody neutralizing scavenger receptor SR-PSOX/CXCL16 while the stimulatory activity of deacylated ManLAM was reversed by an antibody neutralizing class B scavenger receptor CD36. Our data suggest that CD36 mediates the activity of ManLAM and its deacylated form leading to TNF-α release in LPS-stimulated J774 cells and peritoneal murine macrophages, while NO production is modulated by unknown scavenger receptors.
authors.affiliation: Nencki Institute of Experimental Biology, Laboratory of Plasma Membrane Receptors, 3 Pasteur St., 02-093 Warsaw, Poland.
authors.forename: Szczepan
authors.initials: S
authors.lastname: Józefowski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Sobota
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pawłowski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kwiatkowska
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis; D018955:CD36 Antigens / Q000378:metabolism; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology; D004357:Drug Synergism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000378:metabolism; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000942:Antigens, Bacterial; D018955:CD36 Antigens; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D037601:Mannose-Binding Lectin; D051116:Receptors, Scavenger; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C050016:lipoarabinomannan; D009569:Nitric Oxide; D016264:Dextran Sulfate