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.
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.
Luna
Gonzalo
G
Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas 1020-A, Venezuela.
Paez
Jesus
J
Cardier
José E
JE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000950:Antigens, Ly / Q000096:biosynthesis*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007249:Inflammation; D020382:Interleukin-18 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D020382:Interleukin-18; D015850:Interleukin-6; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor