Activation of mouse natural killer T cells accelerates liver regeneration after partial hepatectomy.
Gastroenterology
; 131(5): 1573-83, 2006 Nov.
Article
en En
| MEDLINE
| ID: mdl-17064698
ABSTRACT
BACKGROUND & AIMS:
Activation of natural killer T cells with the synthetic ligand alpha-galactosylceramide (alpha-GalCer) induced hepatotoxicity through the tumor necrosis factor (TNF) and Fas-ligand-mediated pathway in aged mice. The aim of this study was to elucidate how alpha-GalCer-activated natural killer T cells function in hepatocyte proliferation and liver regeneration in partially hepatectomized (PHx) mice.METHODS:
Mice were injected with alpha-GalCer at 36 hours after 70% PHx. Hepatocyte mitosis was evaluated by either mitotic figures or proliferating cell nuclear antigen staining. The role of TNF and Fas-ligand in hepatocyte mitosis also was assessed.RESULTS:
In PHx mice injected with alpha-GalCer, hepatocyte mitosis was greatly enhanced at 44 hours after surgery and the increase was more obvious in aged mice than in young mice. The expression of both TNF receptor 1 and Fas-ligand in liver natural killer T cells tended to increase after alpha-GalCer injection in PHx mice. Treatment of mice with anti-NK1.1 Ab 3 days before and just after hepatectomy greatly inhibited the effect of alpha-GalCer on hepatocyte mitosis and liver regeneration. Furthermore, pretreatment of PHx mice with either anti-TNF Ab or anti-FasL Ab 1 hour before alpha-GalCer injection mostly abrogated the increase in hepatocyte proliferation. alpha-GalCer injection did not accelerate hepatocyte proliferation in Fas-mutated lpr mice after PHx. CD1d-/- mice without alpha-GalCer injection showed decreased hepatocyte mitosis after PHx.CONCLUSIONS:
Activated natural killer T cells help hepatocyte proliferation and liver regeneration after PHx via the TNF and Fas/Fas-ligand-mediated pathway.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
/
Activación de Linfocitos
/
Regeneración Hepática
Límite:
Animals
Idioma:
En
Revista:
Gastroenterology
Año:
2006
Tipo del documento:
Article
País de afiliación:
Japón