Journal of hepatology · 2006
Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства 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.
Melhem Alaa, Muhanna Nidal, Bishara Amal, Alvarez Carlos E, Ilan Yaron, Bishara Taiser, Horani Amjad, Nassar Mithal, Friedman Scott L, Safadi Rifaat
Аннотация
BACKGROUND/AIMS: We have investigated the role of natural killer (NK) cells in hepatic fibrogenesis. Mouse NK cells express both inhibitory/activating-killing-immunoglobulin-related-receptors (iKIR/aKIR) specific for Class-I-molecules.
METHODS: Hepatic fibrosis induced by carbon-tetrachloride (CCl4) was compared between wild-type (WT) male-BALBc; combined-immunodeficiency (SCID, lacking B/T-cells); and SCID-BEIGE-mice (lacking B/T/NK cells), and naive mice.
RESULTS: Hepatic fibrosis significantly increased in all CCl4-treated groups. SCID-BEIGE mice had more fibrosis than SCID-mice (P<0.0001) as assessed by morphometry of sirius-red stained tissue sections. Following fibrosis, hepatic NK cells significantly decreased, the aKIR:iKIR-ratio significantly increased while Class-I expression on HSC decreased (P<0.001). Both freshly isolated and in situ HSC displayed a significant increase in cellular apoptosis following fibrosis induction. Confocal microscopy demonstrated the direct adhesion of NK cells to HSC in mouse liver sections and in vitro human NK/HSC co-culture. In human HSC there was decreased Class-I expression and increased apoptosis as well, which was further increased following blocking of either HSC-related Class-I or NK-related killer inhibitory receptors. Apoptosis was inhibited by pre-incubation of NK cells with the granzyme inhibitor 3,4-dichloroisocoumarin.
CONCLUSIONS: During liver injury, NK cells have an anti-fibrotic activity at least in part through stimulation of HSC killing.
METHODS: Hepatic fibrosis induced by carbon-tetrachloride (CCl4) was compared between wild-type (WT) male-BALBc; combined-immunodeficiency (SCID, lacking B/T-cells); and SCID-BEIGE-mice (lacking B/T/NK cells), and naive mice.
RESULTS: Hepatic fibrosis significantly increased in all CCl4-treated groups. SCID-BEIGE mice had more fibrosis than SCID-mice (P<0.0001) as assessed by morphometry of sirius-red stained tissue sections. Following fibrosis, hepatic NK cells significantly decreased, the aKIR:iKIR-ratio significantly increased while Class-I expression on HSC decreased (P<0.001). Both freshly isolated and in situ HSC displayed a significant increase in cellular apoptosis following fibrosis induction. Confocal microscopy demonstrated the direct adhesion of NK cells to HSC in mouse liver sections and in vitro human NK/HSC co-culture. In human HSC there was decreased Class-I expression and increased apoptosis as well, which was further increased following blocking of either HSC-related Class-I or NK-related killer inhibitory receptors. Apoptosis was inhibited by pre-incubation of NK cells with the granzyme inhibitor 3,4-dichloroisocoumarin.
CONCLUSIONS: During liver injury, NK cells have an anti-fibrotic activity at least in part through stimulation of HSC killing.