title: Lipoarabinomannan, a possible virulence factor involved in persistence of Mycobacterium tuberculosis within macrophages.
abstract: Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis and leprosy, respectively, produce large quantities of lipoarabinomannan (LAM), a highly immunogenic, cell wall-associated glycolipid. This molecule has been previously reported to be a potent inhibitor of gamma interferon-mediated activation of murine macrophages. Studies of the mechanism by which this mycobacterial glycolipid down-regulates macrophage effector functions provide evidence that LAM acts at several levels and that it can (i) scavenge potentially cytotoxic oxygen free radicals, (ii) inhibit protein kinase C activity, and (iii) block the transcriptional activation of gamma interferon-inducible genes in human macrophage-like cell lines. These results suggest that LAM can inhibit macrophage activation and triggering and cytocidal activity and that it may represent a chemically defined virulence factor contributing to the persistence of mycobacteria within mononuclear phagocytes.
authors.affiliation: Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark 07103.
authors.forename: J
authors.initials: J
authors.lastname: Chan
authors.forename: X D
authors.initials: XD
authors.lastname: Fan
authors.forename: S W
authors.initials: SW
authors.lastname: Hunter
authors.forename: P J
authors.initials: PJ
authors.lastname: Brennan
authors.forename: B R
authors.initials: BR
authors.lastname: Bloom
mesh_terms: D002478:Cells, Cultured; D016166:Free Radical Scavengers; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013481:Superoxides / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014774:Virulence
chemical_list: D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; C050016:lipoarabinomannan; D013481:Superoxides; D007371:Interferon-gamma; D011493:Protein Kinase C