Transplantation · 1999
HLA-G expression protects porcine endothelial cells against natural killer cell-mediated xenogeneic cytotoxicity.
СтатьяПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sasaki H, Xu X C, Smith D M, Howard T, Mohanakumar T
Аннотация
BACKGROUND: Natural killer (NK) cells are major component of the cellular response in xenotransplantation. NK cell activation and NK cell-mediated cytotoxicity can be a direct barrier to the potential use of xenogeneic organs in human transplantation.
METHODS: To determine if HLA-G would protect porcine xenogeneic cells from human NK cell lysis, human full-length HLA-G genomic DNA was transfected into porcine aortic endothelial cell (PAECs) by the lipofection method. Surface expression of HLA-G in transfected PAECs was confirmed by immunofluorescense staining with anti-HLA class I framework antibody, PA2.6. Fresh human peripheral blood lymphocytes were used as NK effector cells with HLA-G-transfected PAECs as targets in a 51Cr release assay. The inhibition of human polyclonal NK cells by HLA-G expression on PAECs was confirmed by antibody blocking using purified F(ab')2 portion of anti-human HLA class I antibody PA2.6.
RESULTS: Expression of HLA-G on PAECs conferred a significant protection against NK-mediated lysis (range: 52-100% inhibition) when peripheral blood lymphocytes from seven healthy donors, bearing either homozygous HLA-Cw3 or -Cw4 used as NK effector cells. Such protection was inhibited by purified F(ab')2 portion of anti-HLA class I antibody, indicating that the protection of PAECs was directly mediated by HLA-G expression.
CONCLUSIONS: Expression of HLA-G on PAECs protected xenogeneic PAECs against human polyclonal NK cell-mediated lysis. These results indicate that the expression of HLA-G alone in the absence of other nonclassical HLA class I molecules is sufficient to inhibit human NK cell lysis. These findings suggest methods utilizing HLA-G to overcome NK cell-mediated cytotoxicity against porcine endothelial cells, considered the first cell type effected during xenograft cellular rejection.
METHODS: To determine if HLA-G would protect porcine xenogeneic cells from human NK cell lysis, human full-length HLA-G genomic DNA was transfected into porcine aortic endothelial cell (PAECs) by the lipofection method. Surface expression of HLA-G in transfected PAECs was confirmed by immunofluorescense staining with anti-HLA class I framework antibody, PA2.6. Fresh human peripheral blood lymphocytes were used as NK effector cells with HLA-G-transfected PAECs as targets in a 51Cr release assay. The inhibition of human polyclonal NK cells by HLA-G expression on PAECs was confirmed by antibody blocking using purified F(ab')2 portion of anti-human HLA class I antibody PA2.6.
RESULTS: Expression of HLA-G on PAECs conferred a significant protection against NK-mediated lysis (range: 52-100% inhibition) when peripheral blood lymphocytes from seven healthy donors, bearing either homozygous HLA-Cw3 or -Cw4 used as NK effector cells. Such protection was inhibited by purified F(ab')2 portion of anti-HLA class I antibody, indicating that the protection of PAECs was directly mediated by HLA-G expression.
CONCLUSIONS: Expression of HLA-G on PAECs protected xenogeneic PAECs against human polyclonal NK cell-mediated lysis. These results indicate that the expression of HLA-G alone in the absence of other nonclassical HLA class I molecules is sufficient to inhibit human NK cell lysis. These findings suggest methods utilizing HLA-G to overcome NK cell-mediated cytotoxicity against porcine endothelial cells, considered the first cell type effected during xenograft cellular rejection.