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Induction of Mycobacterium avium growth restriction and inhibition of phagosome-endosome interactions during macrophage activation and apoptosis induction by picolinic acid plus IFN gamma

Title
Induction of Mycobacterium avium growth restriction and inhibition of phagosome-endosome interactions during macrophage activation and apoptosis induction by picolinic acid plus IFN gamma
Type
Article in International Scientific Journal
Year
2004
Authors
Pais, TF
(Author)
Other
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Appelberg, R
(Author)
ICBAS
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Journal
Title: MicrobiologyImported from Authenticus Search for Journal Publications
Vol. 150
Pages: 1507-1518
ISSN: 1350-0872
Scientific classification
FOS: Natural sciences > Biological sciences
Other information
Authenticus ID: P-000-ANR
Abstract (EN): Treatment of mouse macrophages with picolinic acid (PA) and gamma-interferon (IFNgamma) led to the restriction of Mycobacterium avium proliferation concomitant with the sequential acquisition of metabolic changes typical of apoptosis, mitochondrial depolarization, annexin V staining and caspase activation, over a period of up to 5 days. However, triggering of cell death by ATP, staurosporine or H2O2 failed to affect mycobacterial viability. In contrast to untreated macrophages where extensive interactions between phagosomes and endosomes were observed, phagosomes from treated macrophages lost the ability to acquire endosomal dextran. N-Acetylcysteine was able to revert both the anti-mycobacterial activity of treated macrophages as well as the block in phagosome-endosome interactions. The treatment, however, induced only a minor increase in the acquisition of lysosomal markers, namely Lamp-1, and did not increase to any great extent the acidification of the phagosomes. These data thus suggest that the anti-mycobacterial activity of PA and IFNy depends on the interruption of intracellular vesicular trafficking, namely the blocking of acquisition of endosomal material by the microbe.
Language: English
Type (Professor's evaluation): Scientific
Contact: rappelb@ibmc.up.pt
No. of pages: 12
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