Expression of the Hematopoietic Stem Cell Antigen Sca-1 (LY-6A/E) in Liver Sinusoidal Endothelial Cells: Possible Function of Sca-1 in Endothelial Cells

Abstract

Several reports have shown that the expression of Sca-1 (Ly-6A/E), the most widely used murine hematopoietic stem cell marker, is restricted to blood vessels in several nonhematopoietic tissues. However, there is no information about which components are expressing Sca-1, and what the role of Sca-1 could be. Because we have previously shown that murine liver endothelial cells from the hepatic sinusoid (LSEC) express some HSC markers (i.e., CD34 and c-kit), we hypothesized that these cells could also express Sca-1. In this work, we show that Sca-1 is constitutively expressed in LSEC, as well as in the liver sinusoid lumen. The expression of Sca-1 in LSEC was confirmed at the mRNA and protein level by reverse transcriptase (RT)-PCR, flow cytometry, and immunofluorescence studies. The expression of Sca-1 was enhanced on the surface of LSEC by tumor necrosis factor (TNF). We examined whether Sca-1 ligation on the surface of LSEC regulates some biological response in these cells. Our results show that ligation of Sca-1 by the anti-Ly-6A/E monoclonal antibody (mAb) D7 stimulated the growth of LSEC and the production of interleukin-6 (IL-6) by these cells. To our knowledge, this is the first report that LSEC express Sca-1, which may constitute additional support to the theory of a common progenitor for the hematopoietic and endothelial cells. Our results show a novel role of Sca-1, indicating that it induces activation of LSEC to proliferate and to produce IL-6. These results suggest that Sca-1 may participate in several clinical conditions such as angiogenesis and inflammation.