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Laboratory of Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal
The effects of picolinic acid (PA) on the intramacrophagic growth
of Mycobacterium avium were studied. PA reduced
M. avium growth inside mouse macrophages and led to a
complete control of mycobacterial growth when added together with
IFN-
. The mechanism involved did not require TNF-
, NO, or the
respiratory burst, and was not dependent on either iron or zinc
withholding. The mycobacteriostatic activity of the macrophages was
associated with the induction of morphological changes that culminated
in apoptosis at day 4 of treatment. PA alone induced apoptosis in
macrophages, and this effect was increased by IFN- treatment.
Apoptosis at day 4 of infection was reduced by inhibiting macrophage
activation with the prostaglandin 15 deoxy-prostaglandin J2
or by treating the cells with the antioxidant
N-acetylcysteine. Mycobacterial growth was partially
restored in macrophages treated with PA and IFN- when 15
deoxy-prostaglandin J2 was added, concomitant with a delay
in apoptosis. N-Acetylcysteine or glutathione could also
completely revert the mycobacteriostatic effects of PA or PA plus
IFN-.
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