Adenosine-regulated mechanisms in the pathogenesis of ventilation disorders in patients with pulmonary tuberculosis

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Abstract

Uncovering involvement of the purinergic system in the pathogenesis of ventilation disorders (VD) may provide additional information about the pathophysiological mechanisms leading to the development of VD in pulmonary tuberculosis (PT). The aim was to identify a relationship between the parameters of adenosine metabolism, inflammatory response and altered ventilation metabolism in PT patients. Materials and methods. Obstructive and mixed PT patients were assigned to subgroups with/without VD for assessing adenosine deaminase activity (ADA-1, 2) in serum, mononuclear cells, neutrophils; ecto-5’-nucleotidase (ecto-5’-NT); CD26 (dipeptidyl peptidase-4, DPP-4), phagocyte oxidative burst measured by NO generation. Results. PT patients showed decreased ADA-1 and CD26 (DPP-4), but increased ADA-2. Elevated intracellular adenosine concentration was found in mononuclear cells in patients lacking VD, whereas patients with mixed and obstructive VD — had it in neutrophils. Mononuclear cells of patients with PT lacking VD as well as with obstructive VD type had decreased NO3– concentration. Neutrophil hyperactivity was recorded in all groups of PT patients. Patients with PT lacking VD as well as with mixed VD type showed that the parameters of external respiration were associated with activity of extra-/intracellular ADA, whereas obstructive VD was caused by excessive formation of serum adenosine. Changes in respiratory function in PT were associated with decreased level of serum NO radicals, impaired nitrogen-dependent bactericidal phagocyte activity, and overproduced neutrophil oxygen radicals. Conclusion. Purinergic regulation is involved in regulating inflammatory and compensatory processes in PT patients as well as impaired ventilation efficiency. The most severe respiratory disorders observed in PT patients with mixed VD type are associated with the most prominent changes in nucleotidase activity, particularly ecto-ADA-2 and DPP-4/CD26.

About the authors

M. E. Dyakova

St. Petersburg Research Institute of Phthisiopulmonology

Author for correspondence.
Email: marinadyakova@yandex.ru
ORCID iD: 0000-0002-7810-880X

Marina E. Dyakova,  PhD (Biology), Senior Researcher 

194064, St. Petersburg, Ligovskiy pr., 2–4

Phone: +7 921 375-54-32 

Russian Federation

N. B. Serebryanaya

St. Petersburg State University; North-Western State Medical University named after I.I. Mechnikov; Institute of Experimental Medicine

Email: nbvma@mail.ru
ORCID iD: 0000-0002-2418-9368

PhD, MD (Medicine), Professor of the Department of Cytology and Histology, Faculty of Biology; Professor of the Department of Clinical Mycology, Allergology and Immunology; Leading Researcher, Laboratory of Immunopathophysiology, Department of General Pathology and Pathophysiology

St. Petersburg 

Russian Federation

L. D. Kiryukhina

St. Petersburg Research Institute of Phthisiopulmonology

Email: kiryuhina_larisa@mail.ru
ORCID iD: 0000-0001-6550-817X

PhD (Medicine), Leading Researcher, Head of the Department of Functional Diagnostics 

Russian Federation

D. S. Esmedlyaeva

St. Petersburg Research Institute of Phthisiopulmonology

Email: diljara-e@yandex.ru
ORCID iD: 0000-0002-9841-0061

PhD (Biology), Senior Researcher 

St. Petersburg 

Russian Federation

P. K. Yablonskiy

St. Petersburg Research Institute of Phthisiopulmonology; St. Petersburg State University

Email: piotr_yablonskii@mail.ru
ORCID iD: 0000-0003-4385-9643

PhD, MD (Medicine), Professor, Director; Dean of the Medical Faculty 

St. Petersburg 

Russian Federation

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