Adenosine-related mechanisms in the pathogenesis of chronic obstructive pulmonary disease in patients with pulmonary tuberculosis

Abstract

Background: Purine regulation plays an important role in inflammation. Therefore, disclosing the role of purine regulation in the pathogenesis of chronic obstructive pulmonary disease (COPD) may provide additional information about inflammation pathophysiology and compensation, which lead to COPD in chronic inflammation supported by tuberculosis infection.
The aim of this study was to identify the relationship of adenosine metabolic indexes with characteristics of an oxidative burst, nitric oxide generation and functional parameters of external respiration (ER) in patients with pulmonary tuberculosis in combination with COPD.
Materials and methods. The study included male active smokers with a verified diagnosis of pulmonary tuberculosis (PT) and PT in combination with COPD (PT+COPD). Purine metabolism was evaluated by adenosine deaminase (ADA-1 and ADA-2) activity in serum (ecto-ADA), mononuclear cells (mnc), and neutrophils (nph); serum concentration of ecto-5’-nucleotidase (ecto-5’-NT); and serum and mnc concentrations of CD26 (dipeptidyl peptidase-4, DPP-4). Oxidative burst in phagocytes was evaluated by the nitroblue tetrazolium conversion test (NBT-test). Nitric oxide generation – by concentrations of NO metabolites in blood serum, mnc, and nph.
Results. Patients with PT and PT+COPD had multidirectional changes in extracellular adenosine concentration (increased activity of ecto-ADA-2, level of ecto-5’-NT, decreased activity of ecto-ADA-1). At the same time, intracellular adenosine concentrations could be increased (decreased mnc activities of ADA-1 and CD26 (DPP-4)). In patients with PT+COPD, the respiratory burst was observed only in mnc and nph. In patients with PT, increased production of reactive oxygen species was observed only in nph
in the inductive NBT-test. In both groups, the nitrite and nitrate production significantly decreased both in monocytes and nph. In patients with PT, parameters of external respiration (ER) were linked to ecto-5’-NT and nonspecific peptidase CD26 (DPP-4) activities and to nitrite production by nph and monocytes. At the same time, in patients with PT+COPD, ER indexes were linked to monocyte activities of ecto-ADA-1 and ADA-1 and to serum nitrate and nph nitrite.
Conclusion. In PT patients, impaired ER was associated with excessive formation of adenosine and excessive activation of adenosine-forming enzymes, as well as with nitrite production by nph and monocytes, which are active participants in bactericidal reactions directed against mycobacterium tuberculosis (MBT). However, in PT+COPD, the leading factor is impaired adenosine degradation with decreased ADA-1 activity, development of endothelial dysfunction, and changed nph functionality. Therefore, development of targeted means for normalizing the purinergic metabolism in patients with PT, specifically, by increasing the ADA-1 isoform activity, may provide either prevention in COPD or stabilization of the process in patients with already developed pathology.