title: Extrahepatic manifestations in transgenic mice of osteopontin in hepatocytes-A clue to advent of pathological state in various organs of chronic hepatitis C patients.
abstract: Osteopontin is a cytokine essential for initiation of Th1 immune reaction. We established transgenic mice expressing osteopontin in hepatocyte, in which liver necrosis with lymphocyte infiltration developed gradually from 12 weeks of age with up-regulated osteopontin levels in the circulation, suggesting that extrahepatic manifestations might also occur as a result of excessive Th1 immune reaction. We examined histological and immunohistochemical features of various organs in these mice. Splenomegaly and enlargement of lymph nodes around the liver and intestine became apparent with marked infiltration of small lymphocytes in the transgenic mice later than 24 weeks of age. Immunostaining revealed that lymphocytes in the spleen and lymph nodes were positive for either CD3 or CD20, suggesting that the infiltrating lymphocytes were both B and T cells. Similar lymphocyte infiltration was found in the lung, kidney and submandibular gland. Alveolar septa became hypertrophic with lymphocyte infiltration, and the lung showed the appearance of interstitial pneumonia. These lesions are similar to extrahepatic manifestations in chronic hepatitis C patients, suggesting that augmented Th1 immune reaction to hepatitis C virus (HCV) proteins or the proteins with molecular mimicry of HCV may be a contributing factor for the formation of the pathological state not only in the liver but also in various organs under chronic infection of hepatitis C virus.
authors.affiliation: Division of Gastroenterology & Hepatology, Internal Medicine, Saitama Medical School, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Saitoh
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsui
authors.forename: Mie
authors.initials: M
authors.lastname: Inao
authors.forename: Sumie
authors.initials: S
authors.lastname: Mimura
authors.forename: Heasaeng
authors.initials: H
authors.lastname: Koh
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ohno
authors.forename: Sumiko
authors.initials: S
authors.lastname: Nagoshi
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kayano
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mochida
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujiwara