An immunohistochemical and morphometric study of the heterogeneity of sinusoidal endothelial cells in the human liver.

To elucidate the functional heterogeneity of sinusoidal endothelial cells ( SECS) in man, we analyzed immunohistochemically and morphometrically the in tralobular distribution of the functional molecules, CD4, CD14, CD32, CD36, CD54 and venous endothelial antigen (PAL-E) by using indirect horseradish peroxidase (HRP)- or alkaline phosphate labeled antibody method. To disting uish the antigens on SE from these on Kupffer cells, the tissue sections st ained for antigens were doubly stained with the HRP- or FITC-label Bauhinin a purpuria hemoaglutinin (BPA) which specifically reacts with Kupffer cells and neutrophiles. The staining intensity of antigens per unit area was qua ntified by optical density measurement using a computer-assisted image anal ysis system. Upon double-staining with antigens and BPA lectin, all the antigens describ ed above were demonstrated on SECS. CD4, CD14, CD31, CD32, and CD54 were al so detected on Kupffer cells. The staining intensities of CD32 and CD54 on SECs were gradually increased from the periportal area to the central area. Conversely, those of CD4 and CD14 on SECs were gradually decreased from th e periportal area to the central area. CD31 a CD36 were evenly found on the SECs throughout the hepatic lobule. Although the SECs in the outer peripor tal areas did not express CD4, CD14 and CD32, those SECs strongly express t he PAL-E venous antigen, which did not on other SECS, a resided together wi th Kupffer cells. Those results show the presence of two zone-related SE subsets which are qu alitatively different in the expression functional molecules (CD4, CD14 and CD32) and PAL venous antigen, and further indicate the qualitative and zon e-related differences of SECs in the expressions of CD4, CD14, CD32, and CD 54. This heterogeneity of SECs may thus be important in furthering the unde rstanding of hepatic lobule function.