Pathophysiological Mechanisms Destruction of the Lung Connective Tissue in Tuberculosis


Background. The restructuring of the lung tissue stroma during destructive tuberculosis is one of the most important pathological events in the formation of residual changes in the lung tissue during tuberculosis inflammation. Most patients with tuberculosis have destructive forms of this disease. Therefore, studies of pathomorphological changes in the pulmonary tissue of tuberculosispatients are very relevant. It is known that the formation of decavities in volves the destruction of the extracellular matrix, which includes collagen fibers that support the structure of the lungs. The destruction of this matrix leads to the destruction of lung tissue and is a consequence of the activity of proteinase enzymes. One of the products of the destruction of collagen fibers of the lung tissue is oxyproline and its fractions. It has been proventhatin the lungs collagen fibers break down matrix metalloproteinases (MMPs), which belong to the family of proteinases, and are able to affectall component soft he extracellular matrix. The process of MMP synthesis is regulated at the transcription level, and the irproteolytic activity is controlled by proenzymes, as well as inhibition of active enzymes by endogenous inhibitors, α2-macroglobulin and tissue inhibitors of metalloproteinases (TIMP), which play an important role in fibrosis processes. However, it is important not only the level of MMP, but also their ratio with TIMP. An increase in the level of TIMP over MMP leads to the degradation of capillaries of the interalveolar septa, while the predominance of MMP over TIMP leads to the destruction of the component soft he extracellular matrix. Recent studies indicate the role of aldosterone in the processes of fibrosis. It is able to activate blood monocytes, induce in flammation, lead to impaired fibrinolysis. Also aldosterone is able to enhance the synthesis and accumulation of collagen. Elevated levels of aldosterone, stimulating the growth of smooth muscle fibers, contribute to the development of fibrosis in the lungs. There is evidence that aldosterone is able to enhance the degradation of the extracellular matrix through the activation of MMP.

Conclusions. Thus, the destruction of the extracellular matrixis one of the most important pathological event sin the formation of residual changes in the lung tissue with tuberculous inflammation.

Keywords: tuberculosis, collagen, hydroxyproline, matrix metalloproteinase, inhibit, aldosterone.


Elkington PT, D’Armiento JM, Friedland JS. Tuberculosis immunopathology: the neglected role of extracellular matrix destruction. Science translational medicine. 2011; 3 (71): 71-76.

Jeon DS, et al. Treatment outcome and mortality among patients with multidrug-resistant tuberculosis in tuberculosis hospitals of the public sector. J. Korean Med. Sci. 2011; 26: 33-41.

Sivangala R, et al. Association of cytokine gene polymorphisms in patients with tuberculosis and their household contacts. Scand. J. Immunol. 2014; 79 (3): 197-205.

Lee ЕJ, et al. Comparison of the Effects of Matrix Metalloproteinase Inhibitors on TNF-a Release from Activated Microglia and TNF-a Converting Enzyme Activity. Biomolecules Therapeutics. 2014; 5: 414-419.

Iyer RP, et al. The history of matrix metalloproteinases: milestones, myths, and misperceptions. Heart and Circulatory Physiology. 2012; 17: 919-930.

Zitka O, et al. Matrix Metalloproteinases. Current Medicinal Chemistry. 2010; 17 (31): 3751-3768.

Tarasova LG, Streltsova EN, Kantemirova BI. Immunogenetic preconditions for disruption of collagen metabolism in tuberculosis. Tuberculosis and lung diseases. 2015; 11: 4-9.

Kim SE, et al. Simvastatin inhibits induction of matrix metalloproteinase‑9 in rat alveolar macrophages exposed to cigarette smoke extract. Exp. Mol. Med. 2009; 41(4): 277-287.

Bellayr IH, Mu X, Li Y. Biochemical insights into the role of matrix metalloproteinases in regeneration: challenges and recent developments. Future Med. Chem. 2009; 1: 1095-1111.

Green JA, et al. In an in vitromodel of human tuberculosis, monocytemicroglial networks regulate matrix metalloproteinase‑1 and -3 gene expression and secretion via a p38 mitogen activated protein kinasedependent pathway. J. Neuroinflammadon. 2013; 10: 107.

Brew K, Nagase H. The tissue inhibitors of metalloproteinases (TIMPs): аn ancient family with structural and functional diversity. Biochimicaet Biophysica Acta. 2010; 1830 (1): 55-71.

El Margoushy NM, Khallel AT. Metalloproteinase and tissue inhibitor of metalloproteinase in tuberculosis and malignant pleuraleffusion. Egyptian Journal of Chest Diseases and Tuberculosis. 2013; 62: 235-240.

Vatansever S, et al. Potential role of matrix metalloproteinase‑2, -9 and tissue inhibitor of metalloproteinases: structure, function, and biochemistry. Clinical and Investigative Medicine. 2009; 4: 293-300.

Cao J, Zucker S. Biology and chemistry of matrix metalloproteinases (MMPs) URL http: // = resource&rid = 11034. (доступ від 26.12.2014).

Volkman HE, et al. Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium. Science. 2010; 327: 466-469.

Coussens A, et al. 1-alpha,25-dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection. Immunology. 2009;127 (4): 539-548.

Seredyuk V. Role of Aldosterone, Mutogenic Growth Factors, ApoptosismInducers and Pulmonary Arterial Hypertension in the Formation and Progression of Chronic Pulmonary Heart Disease. The Pharma Innovation Journal. 2013; 5 (2): 36-40.

Barbera JA, Blanco I. Pulmonary hypertension in patients with chronic obstructive pulmonary disease: advances in pathophysiology and management. Drugs. 2009; 9 (69): 1153-1171.

Hung CS, et al. Aldosterone Induces Tissue Ingibitor of Metalloproteinases‑1 Expression and further Contributes to Collagen Accumulation. Hypertension. 2016; 4 (67): 1309-1320.

Feshchenko YI, Todoriko LD, Kuzhko MM, Gumeniuk MI. Pathomorphosis of tuberculosis - the realities of today, chemoresistance as a sign of progression. Ukr. pulmonol. J. 2018; 2: 6-10.

How to Cite
Shevchenko, O. S., Ovcharenko, I. A., & Todoriko, L. D. (2019). Pathophysiological Mechanisms Destruction of the Lung Connective Tissue in Tuberculosis. Infusion & Chemotherapy, (2), 14-20.

Author Biographies

O. S. Shevchenko, Kharkiv National Medical University, Kharkiv, Ukraine

Shevchenko Olga Stanislavivna
Head of the Department of Phthisiology and Pulmonology,
Doctor of Medical Sciences, professor
4 Avenue of Science, Kharkiv, 61022, Ukraine

I. A. Ovcharenko, Kharkiv National Medical University, Kharkiv, Ukraine

Ovcharenko Iryna Anatoliivna
Assistant of the Department of phthisiology and pulmonology
4 Avenue of Science, Kharkiv, 61022, Ukraine

L. D. Todoriko, Bukovinian State Medical University, Chernivtsi, Ukraine

Todoriko Liliіa Dmytrivna
Нead of the Department of Phthisiology & Pulmonology
MD, professor.
2 Theatralna sq., Chernivtsi, 58002, Ukraine