Document Detail

Necrosis of lung epithelial cells during infection with Mycobacterium tuberculosis is preceded by cell permeation.
MedLine Citation:
PMID:  11035739     Owner:  NLM     Status:  MEDLINE    
Mycobacterium tuberculosis establishes infection, progresses towards disease, and is transmitted from the alveolus of the lung. However, the role of the alveolar epithelium in any of these pathogenic processes of tuberculosis is unclear. In this study, lung epithelial cells (A549) were used as a model in which to examine cytotoxicity during infection with either virulent or avirulent mycobacteria in order to further establish the role of the lung epithelium during tuberculosis. Infection of A549 cells with M. tuberculosis strains Erdman and CDC1551 demonstrated significant cell monolayer clearing, whereas infection with either Mycobacterium bovis BCG or Mycobacterium smegmatis LR222 did not. Clearing of M. tuberculosis-infected A549 cells correlated to necrosis, not apoptosis. Treatment of M. tuberculosis-infected A549 cells with streptomycin, but not cycloheximide, demonstrated a significant reduction in the necrosis of A549 cell monolayers. This mycobacterium-induced A549 necrosis did not correlate to higher levels of intracellular or extracellular growth by the mycobacteria during infection. Staining of infected cells with propidium iodide demonstrated that M. tuberculosis induced increased permeation of A549 cell membranes within 24 h postinfection. Quantitation of lactate dehydrogenase (LDH) release from infected cells further demonstrated that cell permeation was specific to M. tuberculosis infection and correlated to A549 cellular necrosis. Inactivated M. tuberculosis or its subcellular fractions did not result in A549 necrosis or LDH release. These studies demonstrate that lung epithelial cell cytotoxicity is specific to infection by virulent mycobacteria and is caused by cellular necrosis. This necrosis is not a direct correlate of mycobacterial growth or of the expression of host cell factors, but is preceded by permeation of the A549 cell membrane and requires infection with live bacilli.
K M Dobos; E A Spotts; F D Quinn; C H King
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Infection and immunity     Volume:  68     ISSN:  0019-9567     ISO Abbreviation:  Infect. Immun.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-11-15     Completed Date:  2000-11-15     Revised Date:  2013-04-17    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6300-10     Citation Subset:  IM    
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30303, USA.
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MeSH Terms
Cells, Cultured
Cycloheximide / pharmacology
DNA / metabolism
Epithelial Cells / microbiology,  pathology
Histones / metabolism
L-Lactate Dehydrogenase / secretion
Lung / microbiology*,  pathology*
Mycobacterium tuberculosis / growth & development,  pathogenicity*
Streptomycin / pharmacology
Tuberculosis / pathology
Grant Support
Reg. No./Substance:
0/Histones; 57-92-1/Streptomycin; 66-81-9/Cycloheximide; 9007-49-2/DNA; EC Dehydrogenase

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