Oxidative Stress and Free-Radical Oxidation in BCG Granulomatosis Development

Elena Menshchikova,Victor Tkachev,Liliya Cherdantseva,Oksana Potapova,Nikolay Zenkov,Vyacheslav Shkurupiy

doi:10.1155/2013/452546

Abstract

Background. Little is known about the role of free-radical and oxidative stress signaling in granuloma maturation and resolution. We aimed to study the activity of free-radical oxidation processes in the dynamics of BCG-induced generalized granulomatosis in mice. Methods. Chronic granulomatous inflammation was induced in male BALB/c mice by intravenously injecting the BCG vaccine, and the production of oxidative stress (activity of free-radical oxidation processes) and histological changes in the lungs, liver, and peritoneal exudate were measured 3, 30, 60, and 90 days after infection. Results. The tuberculous granuloma numerical density and diameter continuously increased from day 30 to day 90, and the macrophage content within the granulomas progressively diminished with a concomitant elevation in the number of epithelioid cells. The activity of the free-radical oxidation processes in the liver (i.e., the intensity of the homogenate chemiluminescence) reached a maximum at postinfection day 60 and subsequently began to decrease. The peak generation of reactive oxygen species by phagocytes in the peritoneal exudate (measured using flow cytometry) was also shifted in time and fell on day 30. Conclusions. The rise in the steady-state concentration of H2O2 in the liver of mice with BCG-induced granulomatosis is not related to local H2O2 production by phagocytes, and a decrease in the severity of generalized inflammation precedes the resolution of local inflammation.

Highlights

The generation of inflammatory granulomas that result from the proliferation and transformation of phagocytic cells is a hallmark of many infectious (e.g., tuberculosis (TB) and tularemia) and noninfectious diseases [1, 2]
M. bovis bacteria were detected in the foci of the granulomatous inflammation
The study of granulomatous inflammation focuses on cytokine regulation despite the nosological identification of hereditary chronic granulomatous disease, which is based on a variety of defects in the membrane NAD(P)H oxidase complex, resulting in phagocytic cells that cannot generate superoxide anion radicals [11]

Summary

Introduction

The generation of inflammatory granulomas that result from the proliferation and transformation of phagocytic cells is a hallmark of many infectious (e.g., tuberculosis (TB) and tularemia) and noninfectious (e.g., silicosis, asbestosis, and granulomatous hepatitis) diseases (more than 70 disease entities) [1, 2]. The appearance of idiopathic granulomas with an inducer of unknown nature is a distinguishing feature of sarcoidosis, Wegener’s disease, and several other diseases [2, 3] Another problem is the almost complete lack of effective tools and techniques to influence granulomatous processes; anything offered by modern medicine is essential either the therapeutic removal of an inducer (for infectious granulomas) or the surgical removal of the affected organ. We aimed to study the activity of free-radical oxidation processes in the dynamics of BCG-induced generalized granulomatosis in mice. Chronic granulomatous inflammation was induced in male BALB/c mice by intravenously injecting the BCG vaccine, and the production of oxidative stress (activity of free-radical oxidation processes) and histological changes in the lungs, liver, and peritoneal exudate were measured 3, 30, 60, and 90 days after infection. The rise in the steady-state concentration of H2O2 in the liver of mice with BCG-induced granulomatosis is not related to local H2O2 production by phagocytes, and a decrease in the severity of generalized inflammation precedes the resolution of local inflammation

Objectives

Methods

Results

Discussion

Conclusion