Effects of mycobacteria on regulation of apoptosis in mononuclear phagocytes
| Autor: | William N. Rom, K M Tchou-Wong, C Chi, Brändli O, K Klingler, C Aston, R Kim |
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| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Programmed cell death
Immunology Apoptosis Inhibitor of apoptosis Microbiology Mycobacterium Mycobacterium tuberculosis In vivo Macrophages Alveolar medicine Macrophage Humans Cells Cultured Mycobacterium Infections TUNEL assay biology Monocyte biology.organism_classification Molecular biology Infectious Diseases medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Parasitology Research Article |
| Popis: | Since apoptosis is observed in tuberculous granulomata, we investigated the molecular mechanisms underlying the apoptotic pathway in an in vitro model of mycobacterial infection of mononuclear phagocytes. We postulated that Mycobacterium tuberculosis could trigger the apoptotic pathway in macrophages, resulting in death of the microorganism by modulating the expression of bcl-2, bax, bcl-xL, and bcl-xS. We found that the mRNA of bcl-2, an inhibitor of apoptosis, was downregulated in peripheral blood monocytes (PBM) between 2 and 6 h following infection with M. bovis BCG or induction with heat-killed M. tuberculosis H37Ra. Western analysis showed a downregulation of the Bcl-2 protein, with a half-life of 24 h. At the same time points, there was no change in the expression of Bax or Bcl-xS, inducers of apoptosis, but Bcl-xL, another inhibitor of apoptosis, was minimally upregulated by BCG. To determine if apoptosis could be a mechanism for growth inhibition in vivo, we obtained alveolar macrophages by bronchoalveolar lavage from involved sites in patients with active pulmonary tuberculosis. Using the TUNEL (terminal deoxynucleotidyltransferase mediated nick end labeling) technique, we observed significantly more apoptosis in involved segments of five tuberculosis patients (14.8 +/- 1.9%) than in those of normal controls ( |
| Databáze: | OpenAIRE |
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