Peroxynitrite in Sarcoidosis: Relation to Mycobacterium Stationary Phase

There is evidence that the same mycobacterial heat shock proteins (Mtb-HSPs), especially HSP16, the main marker of mycobacteria dormant stage, occur in sarcoid tissues and in circulated immune complexes and prompt the immune responses against the different genetic background, leading to the development of acute sarcoidosis (SA)/Löfgren syndrome, chronic SA, latent tuberculosis (TB), or active TB. In SA there is increased monocytes phagocytic activity, decreased clearance of antigens/immune complexes by monocytes, which are resistant to apoptosis, and decreased serum microbicidal/degradable nitrate⁄nitrite (NOx) concentration. Reduction in NOx may result from the reaction of NOx with superoxide with subsequent production of peroxynitrite (ONOO-). In this study, therefore, we evaluated NOx and ONOO- levels in supernatants of peripheral blood mononuclear cells cultures treated with Mtb-HSPs from 20 SA patients, 19 TB patients, and 21 healthy volunteers using Griess and rhodamine fluorescence methods. We found significantly greater NOx and ONOO- concentrations with/without Mtb-HSPs stimulation in SA and TB patients than in controls. However, there were significantly lower NOx and higher ONOO- levels after Mtb-HSPs induction in SA than TB patients. In summary, in contrast to active TB, increased ONOO- concentration may explain the low level of NOx with induction of M. tuberculosis genetic dormancy program via higher Mtb-HSP16 expression in SA.