Mice lacking TNF?a receptors 1 and 2 are resistant to death and fulminant liver injury induced by agonistic anti-Fas antibody

COSTELLI P; AOKI MP; CARBÓ N; REFFO P; LOPEZ SORIANO FJ; BONELLI G; ARGUILÉS JM; BACCINO FM

NATURE PUBLISHING GROUP

Año: 2003 vol. 10 p. 997 - 997

p style="margin: 0cm 0cm 0pt;" class="MsoNormal">The liver is particularly susceptible to Fas-mediated cytotoxicity. Mice given an adequate parenteral dose of agonistic anti- Fas antibody (aFas) or of FasL are known to develop a devastating liver injury and to die in a few hours. The present work shows that mice lacking TNFR1 and TNFR2 (R[1]) both survive a single dose of aFas, otherwise rapidly lethal, and develop a mild form of hepatic damage, compared to the much more severe liver injury that in a few hours strikes wildtype mice (Rþ), eventually involving increased activity of proteases of different families (caspase 3-, 8-, and 9-like, calpains, cathepsin B). Neither the overall tissue levels of Fas and FasL nor Fas expression at the hepatocyte surface are altered in the liver of R