Immunopathological mechanisms of toxic damage to the liver, thymus and spleen

Shafigullina Z.A., Danilova I.G.

Institute of Immunology and Physiology Ural Branch of RAS, Yekaterinburg
Ural Federal University named after the First President of Russia B.N. Yeltsin, Institute of Natural Sciences and Mathematics, Yekaterinburg

Objective: to establish the features of the immune response in the early stages of diffuse toxic damage.

Materials and methods. Diffuse toxic liver damage of male Wistar rats was caused by a single intraperitoneal injection of an oil solution of carbon tetrachloride (CCl4) at a dose of 50 mg/100 g. Animals were carried out from the experiment on days 3, 7 and 14. The study included hematological and histological analysis, immunohistochemical (IHC) staining of liver, thymus and spleen tissues, quantitative evaluation of CD3+, CD45RA+ (T-and B-lymphocytes), F4/80+ (macrophages), and HSP70+-cells.

Results. CCl4 administration has been shown to cause structural disorders of liver, thymus, and spleen tissue. In the early stages, there is an increase in CD3+-cells in the liver and spleen, while CD45RA+-cells predominating in the thymus. On the 3rd day after CCl4 administration, the number of F4/80+-cells in the liver increases by 56.7%, in the thymus and spleen by 21% and 19.3%, respectively, there is also an increase in the number of HSP70+-cells roughly 2 times in the liver and thymus, and by 7 times in the spleen.

Conclusion. Hepatotropic poison CCl4 causes damage not only the liver but the organs of immunopoesis. In the early stages of exposure to the toxicant the predominant population is T-lymphocytes (CD3+-cells) in the liver and spleen, and B – lymphocytes (CD45RA+-cells) in the thymus. In all the studied organs, the number of macrophages increases on the 3rd day of the experiment, and significantly decreases at the later term. This fact indicates that macrophages act as a target of toxic effects.

The increase in the number of HSP70+-cells in the liver, thymus, and spleen in response to toxic damage is likely aimed at triggering the repair or elimination of denatured proteins that are toxic to the cell.