Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation
Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation
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DOI：
10.1038/labinvest.2010.40
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发表时间：
2010-04-01
影响因子：
5
通讯作者：
Yagi, Junji
中科院分区：
文献类型：
--
作者：
Haruta, Ikuko;Kikuchi, Ken;Yagi, Junji
在原发性胆汁性肝硬变(PBC)的发病机制中，细菌感染已成为人们关注的焦点。我们早些时候报道，在PBC肝脏受损胆管周围的炎症部位检测到细菌脂磷壁酸，PBC患者血清中显示出高滴度的抗链球菌组蛋白样蛋白。在这里，我们研究了慢性细菌暴露是否会引发正常小鼠的PBC样上皮细胞损伤。BALB/c小鼠反复接种各种细菌8周。在末次接种后1周(组1)、3、4或20个月(长期组；组2)处死小鼠，取标本。在接种中间链球菌(S.I.)的第一组小鼠的肝脏中，细胞主要分布在肝实质上方的胆管周围。第2组接种S.I.的小鼠肝脏仅见门静脉性炎症，未见实质炎症，唾液腺可见导管周围细胞浸润。经皮下注射的第1组和第2组BALB/c小鼠血清均有HuCCT1胆管上皮细胞抗体、抗核抗体和抗gp210抗体，但无抗线粒体抗体。S.I.对组蛋白样DNA结合蛋白的免疫反应性(S.I.-HLP)在S.I.接种第1组和第2组BALB/c小鼠的肝脏中均可在门脉区慢性非化脓性破坏性胆管炎部位周围检测到。此外，抗S.I.-HLP抗体也可与合成的gp210多肽结合。细菌引发了PBC样胆管炎、多灶性上皮炎和自身抗体的产生。细菌可能参与了PBC及其相关的多灶性上皮炎的发病机制。实验室调查(2010年)90577-588；doi：10.1038/Labinvest.2010.40；2010年2月8日在线发布
Bacterial infection has become a focus of attention in the pathogenesis of primary biliary cirrhosis (PBC). We earlier reported that the bacterial lipoteichoic acid was detected at the sites of inflammation around damaged bile ducts in the livers of PBC, and PBC patients' sera showed high titers against streptococcal histone-like protein. Here, we investigated whether chronic bacterial exposure could trigger PBC-like epithelial cell damage in normal mouse. BALB/c mice were repeatedly inoculated with various bacteria for 8 weeks. At 1 week (Group 1) and 3, 4, or 20 months (long term; Group 2) after the final inoculation, mice were killed to obtain samples. In the livers of the Streptococcus intermedius (S.i.)-inoculated mice in Group 1, cellular infiltration was predominantly observed around the bile ducts over the hepatic parenchyma. In the S.i.-inoculated mice in Group 2, portal but not parenchymal inflammation was observed in the livers, and periductal cellular infiltrates were detected in the salivary glands. Both S. i.-inoculated Groups 1 and 2 BALB/c mice sera had antibodies against HuCCT1 biliary epithelial cells, anti-nuclear antibodies, and anti-gp210 antibodies, but not anti-mitochondrial antibodies. Immunoreactivity to histone-like DNA-binding protein of S.i. (S.i.-HLP) was detectable around the sites of chronic nonsuppurative destructive cholangitis in the portal area in the livers of both S. i.-inoculated Groups 1 and 2 BALB/c mice. Furthermore, anti-S.i.-HLP antibody bound to synthetic gp210 peptide, as well. Bacteria triggered PBC-like cholangitis, multifocal epithelial inflammation, and autoantibody production. Bacteria are likely involved in the pathogenesis of PBC and of associated multifocal epithelial inflammation. Laboratory Investigation (2010) 90, 577-588; doi: 10.1038/labinvest.2010.40; published online 8 February 2010