MOLECULAR APOPTOSIS MECHANISMS WITH UNDERLYING EXPERIMENTAL ACUTE LUNG INJURY

Abstract

Background. Current data suggest systemic autoimmune activation in the pathogenesis of bronchopulmonary diseases. The imbalance in the system of pro- and anti-inflammatory cytokines is very important in immunopathogenesis. Objective. The aim of our research was to determine the caspase-3 rate in the dynamics of experimental acute lung injury and to study the relationship between their level and the number of cells carrying membrane binding TNF receptor type 1 to define the main mechanisms of cell death. Results. The analysis of the results of caspase-3 rate in lung homogenate showed that this cysteine proteinase was uniformly increasing in all experimental groups during simulating of ALI induced by administration of hydrochloric acid (p<0.001). When comparing the results of caspase course of apoptosis it was defined that, despite the progressive increase in caspase-3 rate in lung homogenate, cysteine proteinase rate in plasma did not change. The receptor mechanism of apoptosis was studied by establishing correlation relationships with the number of cells carrying membrane binding TNF type 1 (TNF-R1) receptor. A strong positive correlation relationship between the number of neutrophils with TNF-R1 and caspase-3 rate in lungs of all research groups was determined. Conclusions. The implementation of neutrophils death by apoptosis is caused by change of activity of caspase cascade effector components, such as caspase-3, in cases of ALI induced by intratracheal administration of hydrochloric acid. One of the potential mechanisms responsible for the activation of caspase course is excessive generation of active forms of oxygen and increase in the number of neutrophils carrying membrane binding TNF receptor type 1.