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PMID: 1850379 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Lipoarabinomannan, a possible virulence factor involved in persistence of Mycobacterium tuberculosis within macrophages.

Infection and immunity ·Vol. 59 ·No. 5 ·1991-05-00 ·Pages 1755-61

Chan J, Fan XD, Hunter SW, Brennan PJ, Bloom BR

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.

MeSH Terms
Cells, Cultured Free Radical Scavengers Humans Interferon-gamma/pharmacology Lipopolysaccharides/toxicity Macrophages/microbiology Mycobacterium tuberculosis/pathogenicity Protein Kinase C/antagonists & inhibitors Superoxides/metabolism Transcription, Genetic/drug effects Virulence
Chemicals
Free Radical Scavengers Lipopolysaccharides lipoarabinomannan Superoxides Interferon-gamma Protein Kinase C
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chan J
Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark 07103.
Fan X D
Hunter S W
Brennan P J
Bloom B R
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/iai.59.5.1755-1761.1991
Published
1991-05-00
Pages
1755-61
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC257912
Subset
IM
Grants
NIAID NIH HHS · AI 07118 · United States
NIAID NIH HHS · AI 23545 · United States
NIAID NIH HHS · AI 26491 · United States
External Links
PubMed source DOI: 10.1128/iai.59.5.1755-1761.1991 PMC Full Text View journal details
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