Role of CD68+ and CD206+ cells in the progression of toxic liver fibrosis in rats

Abstract

The aim of the work was to evaluate the role of stellate macrophages in a large number of points of toxic liver fibrosis in rats. Liver fibrosis and cirrhosis in male Wistar rats were induced with thioacetamide at a dose of 200 mg/kg animal weight for 17 weeks. Histological preparations of the liver were stained with hematoxylin and eosin according to the Mallory method. Immunohistochemical examination was performed on paraffin sections using monoclonal mouse antibodies CD68 and polyclonal rabbit antibodies CD206. The fibrosis degree was determined according to the Ishak semi-quantitative scale. Toxic liver fibrosis before the start of its transformation into cirrhosis (9 weeks) was accompanied by an increase in the number of CD68+ cells compared with the control. At all subsequent experiment stages, no differences were found in comparison to the control. In the liver of control rats, CD206+ cells were practically absent. Throughout the experiment, their number remained above the control point – 3 weeks. With the progression of liver cirrhosis, a decrease in the number of CD206+ cells was noted, but it did not reach a level of 3 weeks. Morphologically, two different groups of CD68+ cells were identified. One group of cells had a pterygoid shape and they were located mainly in the liver sinusoids. The second group of CD68+ cells had a round shape and different localization. They were detected around the vessels of portal zones, surrounded brown pigment accumulations in connective tissue septa, were observed near single lying groups or groups of giant hepatocytes and liver cells containing brown pigment in the cytoplasm, and were also noted in the foci of necrosis of hepatocytes. Cells, expressing the CD206 marker, are round in shape and are elongated and located in the liver sinusoids. Presumably, round-shaped CD68+ cells perform a phagocytic function, and pterygoid-shaped CD68+ cells transdifferentiate into CD206+ cells that have anti-inflammatory properties.