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Peroxynitrite in Sarcoidosis: Relation to Mycobacterium Stationary Phase

A Dubaniewicz1, L Kalinowski, M Dudziak

  • 1Department of Pulmonology, Medical University of Gdansk, 7 Debinki St., 80-211, Gdansk, Poland, aduban@gumed.edu.pl.

Advances in Experimental Medicine and Biology
|May 29, 2015
PubMed

Insights

Mycobacterial heat shock proteins (Mtb-HSPs) are linked to sarcoidosis (SA) and tuberculosis (TB). Higher peroxynitrite (ONOO-) levels in SA patients suggest Mtb-HSP16 may induce M. tuberculosis dormancy.

Area of Science:

  • Immunology
  • Microbiology
  • Pulmonary Medicine

Background:

  • Mycobacterial heat shock proteins (Mtb-HSPs), particularly HSP16, are implicated in sarcoidosis (SA) and tuberculosis (TB).
  • SA is characterized by altered monocyte function and reduced nitric oxide (NOx) levels, potentially due to peroxynitrite (ONOO-) formation.
  • Mtb-HSPs may trigger immune responses leading to diverse clinical outcomes, including SA and TB.

Purpose of the Study:

  • To investigate the levels of NOx and ONOO- in peripheral blood mononuclear cells (PBMCs) stimulated with Mtb-HSPs in patients with SA, TB, and healthy controls.
  • To explore the role of Mtb-HSPs in the pathogenesis of SA and TB, particularly concerning M. tuberculosis dormancy.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) were cultured from 20 SA patients, 19 TB patients, and 21 healthy volunteers.
  • PBMCs were stimulated with Mtb-HSPs, and NOx and ONOO- levels in supernatants were measured using Griess and rhodamine fluorescence assays.
  • Comparative analysis of NOx and ONOO- concentrations was performed across the three groups, with and without Mtb-HSP stimulation.

Main Results:

  • Both SA and TB patients exhibited significantly higher NOx and ONOO- concentrations compared to healthy controls, both with and without Mtb-HSP stimulation.
  • SA patients showed significantly lower NOx levels and significantly higher ONOO- levels after Mtb-HSP induction compared to TB patients.
  • Elevated ONOO- levels in SA patients following Mtb-HSP stimulation may indicate a mechanism for reduced NOx and the induction of M. tuberculosis dormancy via HSP16.

Conclusions:

  • Increased ONOO- concentration, particularly after Mtb-HSP induction, may be a distinguishing feature of sarcoidosis compared to active tuberculosis.
  • The findings suggest that Mtb-HSP16 could play a role in inducing a dormant M. tuberculosis state in sarcoidosis patients.
  • These results highlight the complex interplay between Mtb-HSPs, immune responses, and disease manifestation in sarcoidosis and tuberculosis.

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