Influence of Cd68 Positive Cells on the Processes of Proliferation and Apoptosis in the Structures of the Respiratory System

Abstract

Aim: To study the influence of macrophages or CD68 positive cells on the processes of proliferation and apoptosis in the respiratory system. Materials and Methods: Experimental modeling of chronic hypoxic hypoxia in combination with inhalation of natural gas was carried out on 133 outbred male rats. Hypoxia was simulated using special seed chambers and natural gas from the Astrakhanskoye Conventional Gas Field at a concentration of 3 mg/m3. The animals were placed under these conditions four hours a day for five days a week for four months. The animals were removed once a month - after 30, 60, 90 and 120 days. The activity of proliferation and apoptosis processes was studied by immunohistochemical method, followed by analysis of the expression of the proliferation marker Ki67, the apoptosis marker p53. The morphofunctional activity of macrophages was determined by the distribution of CD68 positive cells in structural components of respiratory system and the cytokine content in arterial blood taken from the abdominal aorta, that is, at the exit from lungs. Results: With the increase of the chronic experiment duration, the formation of two types of multidirectional morphological changes was revealed: thinning and stretching of the interalveolar septa, an increase in the volume of the alveoli in the peripheral parts of the lungs, and thickening of the interalveolar septa due to increased blood supply and edema-swelling in the early stages and proliferation of fibrous connective tissue in later periods; whereas the diameter and volume of the alveoli became smaller. Under chronic hypoxia combined with the action of natural gas, in all studied structures of the respiratory system there was an increase in the activity of CD68 positive cells. This is manifested by an increase in their number and activation of spontaneous and induced production of the pro-inflammatory cytokine TNFα. Besides, in areas of the lungs with changes in the type of atelectasis, an increase in the expression of the proliferation marker Ki67 and the apoptosis marker p53 was revealed. The latter is most likely associated with a deterioration in blood supply and oxygenation of these areas and the migration of leukocyte and fibroblast cells here, followed by their proliferation and formation pulmonary fibrosis. In areas with emphysematous changes, a decrease in the content of Ki67 positive cells was revealed with a simultaneous increase in the number of p53 positive cells. Conclusion: Thus, it is possible to determine a direct relationship between the increase in the morphofunctional activity of CD68 positive cells and the intensity of proliferation and apoptosis processes in the structural components of the respiratory system under chronic hypoxia combined with natural gas inhalation.