Selective Mycobacterium avium-induced production of nitric oxide by human monocyte-derived macrophages

Infection with a virulent strain of Mycobacterium avium, but not with virulent Mycobacterium tuberculosis or avirulent Mycobacterium smegmatis, induced the formation of nitric oxide by human monocyte-derived macrophages. This process was not affected by lipopolysaccharide or cytokines such as interferon-gamma or tumor necrosis factor alpha. M. avium-induced nitric oxide production was significantly decreased by NG-monomethyl-L-arginine, a potent inhibitor of nitric oxide synthase activity, without any significant enhancement of intramacrophagic mycobacterial growth. Infection with all the three mycobacterial species induced a significant activation of phospholipase A2 activity of macrophages as evidenced by the increased release of thromboxane A2. Finally, nitric oxide production by human monocyte-derived macrophages required infection with live M. avium, as neither gamma-irradiated M. avium nor the subcellular fractions of this microorganism (cell wall, cytosol) were able to trigger nitric oxide synthesis.