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Volume 150, Issue 5

Induction of growth restriction and inhibition of phagosome–endosome interactions during macrophage activation and apoptosis induction by picolinic acid plus IFN Free

Abstract

Treatment of mouse macrophages with picolinic acid (PA) and -interferon (IFN) led to the restriction of 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 HO 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. -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 IFN depends on the interruption of intracellular vesicular trafficking, namely the blocking of acquisition of endosomal material by the microbe.

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  • Accepted:
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  • Published Online:
Keyword(s): FACS, fluorescence-activated cell sorting , IFNγ, γ-interferon , Jc-1, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide , MTT, methylthiazoletetrazolium , PA, picolinic acid , PS, phosphatidylserine and TMR, tetramethylrhodamine
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2004-05-01
2024-04-18
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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 IFNγ
Microbiology 150, 1507 (2004); https://doi.org/10.1099/mic.0.26815-0
/content/journal/micro/10.1099/mic.0.26815-0
/content/journal/micro/10.1099/mic.0.26815-0
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