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Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis.

Abstract
The effect of Mycobacterium tuberculosis infection on the viability of healthy (control) human alveolar macrophages was evaluated by staining with ethidium homodimer and calcein to discriminate live from dead cells. Infection with M. tuberculosis H37Ra or H37Rv increased macrophage mortality at 6 days from the control level of 3.8% +/- 0.7% to 28.7% +/- 6.9% or 12.6% +/- 3.1%, respectively (P < 0.001 for comparisons of all conditions). A role for tumor necrosis factor alpha (TNF-alpha) in the M. tuberculosis-induced cytolysis of alveolar macrophages was demonstrated by increased cytotoxicity following the addition of exogenous TNF-alpha to the cultures and by enhancement of macrophage survival when M. tuberculosis-infected alveolar macrophages were treated with pentoxifylline or anti-TNF-alpha antibody. The cytolytic mechanism was determined to be apoptosis by the demonstration of a characteristic internucleosomal ladder of genomic DNA by agarose gel electrophoresis, by finding nuclear fragmentation and condensation by electron microscopy, and by in situ terminal transferase-mediated nick end labeling of fragmented DNA in alveolar macrophages infected with M. tuberculosis in vitro. The latter technique was employed to reveal extensive apoptosis within caseating granulomas from lung tissue samples from clinical tuberculosis cases. The induction of apoptosis in alveolar macrophages by M. tuberculosis may play a role in the macrophage-pathogen interaction of tuberculosis in vivo.
AuthorsJ Keane, M K Balcewicz-Sablinska, H G Remold, G L Chupp, B B Meek, M J Fenton, H Kornfeld
JournalInfection and immunity (Infect Immun) Vol. 65 Issue 1 Pg. 298-304 (Jan 1997) ISSN: 0019-9567 [Print] United States
PMID8975927 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Tumor Necrosis Factor-alpha
Topics
  • Apoptosis
  • Bronchoalveolar Lavage Fluid (cytology)
  • Cells, Cultured
  • DNA Fragmentation
  • Humans
  • Macrophages, Alveolar (microbiology, pathology)
  • Mycobacterium tuberculosis (pathogenicity)
  • Species Specificity
  • Tumor Necrosis Factor-alpha (biosynthesis)

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