Immunohistochemical Heterogeneity of the Endothelium of Blood and Lymphatic Vessels in the Developing Human Liver and in Adulthood

Abstract

The endothelium of liver sinusoids in relation to the endothelium of other blood vessels has specific antigen expression similar to the endothelium of lymphatic vessels. Bearing in mind that there is no consensus as to the period or intensity of the expression of certain antigens in the endothelium of blood and lymphatic vessels in the liver, the aim of our study was to immunohistochemically investigate the dynamic patterns of the expression of CD31, CD34, D2-40, and LYVE-1 antigens during liver development and in adulthood on paraffin tissue sections of human livers of 4 embryos, 38 fetuses, 6 neonates, and 6 adults. The results show that, in a histologically immature liver at the end of the embryonic period, CD34 molecules are expressed only on vein endothelium localized in developing portal areas, whereby the difference between portal venous branches and CD34-negative central veins belongs to the collecting venous system. In the fetal period, with aging, expression of CD34 and CD31 molecules on the endothelium of central veins and blood vessels of the portal areas increases. Sinusoidal endothelium shows light and sporadic CD34 immunoreactivity in the late embryonic and fetal periods, and is lost in the neonatal and adult periods, unlike CD31 immunoreactivity, which is poorly expressed in the fetal and neonatal periods but is present in adults. The endothelium of sinusoids and lymphatic vessels express LYVE-1, and the endothelium of lymphatic vessels express LYVE-1 and D2-40 but not CD34. Similarity between the sinusoidal and lymphatic endothelium includes the fact that both types are LYVE-1 positive and CD34 negative.

D2-40 Immunoreactivity of Lymphatic Vessels Endothelium and Representation of Lymphatic Vessels in the Liver of Human Fetuses of Different Gestational Age

“…Moreover, it should be stressed that our result about the distribution of D2-40 in the liver at the end of fetal period matches its distribution in the hepatic tissue in adults (17). Recently, utilizing D2-40 on the samples of adult hepatic tissue, Fujii et al (20) have documented podoplanin expression in the lymphatic endothelium, nerve fibers, and mesothelium covering the fibrous capsule and, at the same time, an absence of its expression in any of the cell populations in the liver lobule.…”

“…In support of this finding is the fact that the expression of LYVE-1 molecule, a marker of endothelial cells of lymphatic vessels, gradually increases during the period of fetal development, which confirms the fact of the differentiation of lymphatic endothelial cells (1,17,23,24). It should be noticed that in the liver tissue in the first trimester of development, non-differentiated mesenchymal stellate cells were seen around the structures in portal spaces expressing LYVE-1 and morphologically corresponding to lymph vessels (1,18,24,25).…”

“…Endothelium is a common structural component of lymph vessels and sinusoids of the liver, but during embryonal development it differentiates into two morphologically and functionally different epithelial lines characterized by the expression of different molecules -endothelial cells in the liver sinusoids express, above all, CD31 and CD34 molecules (16,17), while endothelial cells of the lymph vessels express LYVE-1 (8,18,19) and D2-40 molecules (20,21).…”

Distribution of Collagen I, III, and IV and Laminin in the Human Liver during Prenatal Development

“…Immunohistochemistry was used to identify antigen collagen type I, collagen type III, and collagen type IV and laminin Nikolić et al, 2017]. The first step of this method is deparaffinizing the tissue in xylene in a thermostat at 60 ° C. Subsequently, the tissue sections were rehydrated by passing the tissue through descending alcohol concentrations (100, 96, and 70%), after which the samples were immersed in distilled water.…”

“…Fetal endothelial cells, hepatocytes, fibroblasts, and hepatic stellate cells synthesize several ECM components, including collagens I, III, and IV, laminin, and fibronectin [Sudhakaran et al, 1997;Roskams, 2006;Friedman, 2008;Roskams, 2008;Lee and Friedman, 2011]. Compared to adults, the significant expression of laminin, fibronectin, and types I and IV collagen can be observed in the spaces of Disse during liver maturation [Duncan, 2003;Shiojiri and Sugiyama, 2004;CollardeauFrachon and Scoazec, 2008;Wells, 2008;Arimoto et al, 2010;Braet et al, 2012;Nikolić et al, 2017].…”