The Role of Neonatal Gr-1+ Myeloid Cells in a Murine Model of Rhesus-Rotavirus-Induced Biliary Atresia.
Am J Pathol
; 188(11): 2617-2628, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-30201498
ABSTRACT
Activation of innate immunity together with cholangiocyte damage occurs in biliary atresia (BA). However, detailed information on the inflammatory cells involved is lacking. This study investigates both the pathophysiology of CD11b+Gr-1+ cells in a mouse model of BA and their presence in BA patients. CD11b+Gr-1+ cells were targeted by an anti-Ly6G antibody in murine BA induced by inoculation with rhesus rotavirus. Expression of the Ly6G homolog CD177+ was examined in biopsies from BA patients. The symptoms of BA were ameliorated, and survival was prolonged in those mice receiving 5 to 10 µg of antibody per mouse every 3 days for four times compared with the mice treated with virus alone. However, the mice later developed chronic BA with persistent low body weight and jaundice. Hepatic inflammatory cells were reduced compared with acute BA. Blockade of extrahepatic bile ducts occurred, whereas intrahepatic ductules were partially preserved, and a progressive increase in liver fibrosis was observed. High levels of CD11b+Gr-1+ cells were present in these mice. The administration of an anti-Ly6G antibody again in those chronic BA mice reduced jaundice and restored body weight. In BA patients CD177+ cells were highly expressed in the liver. Our data suggest that the chronic mouse BA model shares key characteristics with clinical BA and indicates the importance of CD11b+Gr-1+ cells in the initiation and progression of BA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por Rotavirus
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Atresia Biliar
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Antígenos Ly
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Rotavirus
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Receptores de Superfície Celular
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Células Mieloides
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Modelos Animais de Doenças
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Isoantígenos
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Cirrose Hepática
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Infant
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article