HLA-G1, but Not HLA-G3, Suppresses Human Monocyte/Macrophage-mediated Swine Endothelial Cell Lysis.
The inhibitory function of HLA-G1, a class Ib molecule, on monocyte/macrophage-mediated cytotoxicity was examined. The expression of inhibitory receptors that interact with HLA-G, immunoglobulin-like transcript 2 (ILT2), ILT4, and KIR2DL4 (CD158d) on in vitro-generated macrophages obtained from peripheral blood mononuclear cells and the phorbol 12-myristate 13-acetate (PMA)-activated THP-1 cells were examined by flow cytometry. cDNAs of HLA-G1, HLA-G3, HLA-E, and human β2-microglobulin were prepared, transfected into pig endothelial cells (PECs), and macrophage- and the THP-1 cell-mediated PEC cytolysis was then assessed. In vitro-generated macrophages expressed not only ILT2 and ILT4 but CD158d as well. The transgenic HLA-G1 on PEC indicated a significant suppression in macrophage-mediated cytotoxicity, which was equivalent to that of transgenic HLA-E. HLA-G1 was clearly expressed on the cell surface of PEC, whereas the levels of HLA-G3 were much lower and remained in the intracellular space. On the other hand, the PMA-activated THP-1 cell was less expressed these inhibitory molecules than in vitro-generated macrophages. Therefore, the HLA-G1 on PECs showed a significant but relatively smaller suppression to THP-1 cell-mediated cytotoxicity compared to in vitro-generated macrophages. These results indicate that by generating HLA-G1, but not HLA-G3, transgenic pigs can protect porcine grafts from monocyte/macrophage-mediated cytotoxicity.
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: hiroshieguchi@hotmail.com.
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Eguchi
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Maeda
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Lo
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Matsuura
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Esquivel
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Asada
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Sakai
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Nakahata
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Yamamichi
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Umeda
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Deguchi
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Ueno
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Okuyama
Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Miyagawa
D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D042783:Endothelial Cells / Q000276:immunology; D004727:Endothelium / Q000276:immunology; D005434:Flow Cytometry; D059951:HLA-G Antigens / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D054345:Receptors, KIR2DL4 / Q000378:metabolism; D013552:Swine; D014162:Transfection / Q000379:methods
D015703:Antigens, CD; D016207:Cytokines; D059951:HLA-G Antigens; C515079:KIR2DL4 protein, human; C105299:LILRB1 protein, human; C491341:LILRB2 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D054345:Receptors, KIR2DL4