Abstract
Primary sclerosing cholangitis (PSC) frequently accompanies inflammatory bowel diseases. In an attempt to increase our understanding of the pathogenesis of PSC, we studied bile duct changes in rats with colitis which had been givenn-formyll-methioninel-leucinel-tyrosine (fMLT) rectally; fMLT is one of the chemotactic peptides produced byEscherichia coli, and is secreted into the bile by hepatocytes after it enters the portal blood. Transrectal administration of fMLT induced a marked inflammation in the portal triad and mild hepatocyte necrosis on the 4th day. The infiltrating leukocytes in the portal tract were mostly mononuclear cells, which densely infiltrated around the bile ducts. These mononuclear cells appeared to attach to bile duct epithelial cells, and they were more numerous in the smaller bile ducts. Electron microscopy revealed that lymphocytes were in direct contact with bile duct lining cells and that some epithelial cells had degenerated or collapsed. These results suggest that thisE. coli-derived peptide may induce cholangitis in the small bile duct through cell-mediated mechanisms. Since these pathologic changes resemble those of the bile duct observed in the early stage of PSC, it can be concluded that bacterial chemotactic peptides may play a role in the pathogenesis of small-duct PSC.
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Yamada, S., Ishii, M., Liang, L.S. et al. Small duct cholangitis induced byn-formyll-methioninel-leucinel-tyrosine in rats. J Gastroenterol 29, 631–636 (1994). https://doi.org/10.1007/BF02365447
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DOI: https://doi.org/10.1007/BF02365447