1992 Fiscal Year Final Research Report Summary
Mechanism of bile duct injury in autoimmune cholangitis in senescent mice
| Project/Area Number |
03670364
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Ehime University |
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Principal Investigator |
ONJI Morikazu Ehime Univ. University Hospital, Assistant Professor., 医学部附属病院, 講師 (10112260)
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| Project Period (FY) |
1991 – 1992
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| Keywords | senescent mice / CD8 positive cell / primary biliary cirrhosis |
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| Research Abstract |
The biliary lesions that developed spontaneously in senescent female C57BL/6Nrj mice were investigated. Degeneration of the bile duct epithelium was observed in 12 of 13 mice (92%), destruction of bile duct epithelial cells was seen in 6 of 13 mice (46%) and chronic non-suppurative destructive chonangitis was found in 3 of 13 mice (23%). The biliary lesions were characterized by prominent round cell infiltrates in the portal areas. Extra-hepatic lesions such as sialoadenitits were observed in 6 (46%)and pancreatitis in 7 mice (53%). These lesions were not observed in male C57BL/6, young female C57BL/6, or ICR mice. By transferring the splenic cells of senescent female C57BL/6 mice to 6 week old females, the biliary lesions could be transferred at the rate of 6/9 mice. N418 positive dendritic cells infiltrated into portal areas and their processes contacted with lymphocytes. The lymphocytes infiltrating in the bile ducts were CD8 positive. Moreover, ultrastructural immunocytochemical analysis of lymphocytes infiltrating bile duct epithelia revealed that CD8 positive lymphocytes often formed broad contacts with the epithelial cells. The epithelial cells isolated from gallbladder of young C57BL/6 mice, were cultured with splenic cells of senescent female C57BL/6. Mainly, CD8 positive lymphocytes contacted with cultured epithelial cells of gallbladder. The biliary lesions developing spontaneously in these mice are similar to those found in human primary biliary cirrhosis.
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