Animal models for immune-mediated cholangiopathies

被引:0
|
作者
Ishii, M [1 ]
Ueno, Y [1 ]
Mano, Y [1 ]
Yahagi, K [1 ]
Kobayashi, K [1 ]
Shimosegawa, T [1 ]
Toyota, T [1 ]
机构
[1] Tohoku Univ, Sch Med, Dept Internal Med 3, Aoba Ku, Sendai, Miyagi 9808574, Japan
关键词
apoptosis; carbonic anhydrase; cholangiocyte; Fas; graft vs. host disease; nonsuppurative cholangitis;
D O I
暂无
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Primary biliary cirrhosis (PBC) is an enigmatic chronic liver disease of presumable autoimmune cause. Since a body of evidence obtained from PBC patients has been limited, animal models suitable for analyzing pathogenesis of immune-mediated cholangitis need to be developed. Recent development of cholangiocyte culture has made immunization of animal with cholangiocytes or proteins in cholangiocyte feasible. Immunization with cholangiocytes produced nonsuppurative cholangitis and circulating antibodies reacting to human carbonic anhydrase-II. Immunization of BALB/c mice with human carbonic anhydrase-II produced ductal and periductal inflammation. The sera of immunized BALB/c mice reacted with bile duct cells. This is the first animal model which develops cholangitis by immunization with putative autoantigens. On the other hand, cultured cholangiocytes can be used as target cells for cytotoxic T lymphocytes which may recognize antigens on cholangiocytes. Alloreactive T lymphocytes that were isolated from the liver of GVHD BALB/c mice reproducibly killed BALB/c cholangiocytes. Primary cultured mouse cholangiocytes expressed Fas on their surface constitutively. BALB/c mouse cholangiocytes cocultured with isolated alloreactive T lymphocytes underwent apoptosis. Fas-Fc fusion protein that blocked interaction between Pas and Fas ligand suppressed the cholangiocyte death. Cultured mouse cholangiocytes have enhanced the understanding of the mechanisms of cholangiocyte damage in immune-mediated cholangiopathies.
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收藏
页码:117 / 124
页数:8
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