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Structural changes in the epithelium of the small intestine and immune cell infiltration of enteric ganglia following acute mucosal damage and local inflammation

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Abstract

An acute enteritis is commonly followed by intestinal neuromuscular dysfunction, including prolonged hyperexcitability of enteric neurons. Such motility disorders are associated with maintained increases in immune cells adjacent to enteric ganglia and in the mucosa. However, whether the commonly used animal model, trinitrobenzene sulphonate (TNBS)-induced enteritis, causes histological and immune cell changes similar to human enteric neuropathies is not clear. We have made a detailed study of the mucosal damage and repair and immune cell invasion following intralumenal administration of TNBS. Intestines from untreated, sham-operated and TNBS-treated animals were examined at 3 h to 56 days. At 3 h, the mucosal surface was completely ablated, by 6 h an epithelial covering was substantially restored and by 1 day there was full re-epithelialisation. The lumenal epithelium developed from a squamous cell covering to a fully differentiated columnar epithelium with mature villi at about 7 days. Prominent phagocytic activity of enterocytes occurred at 1–7 days. A surge of eosinophils and T lymphocytes associated with the enteric nerve ganglia occurred at 3 h to 3 days. However, elevated immune cell numbers occurred in the lamina propria of the mucosa until 56 days, when eosinophils were still three times normal. We conclude that the disruption of the mucosal surface that causes TNBS-induced ileitis is brief, a little more than 6 h, and causes a transient immune cell surge adjacent to enteric ganglia. This is much briefer than the enteric neuropathy that ensues. Ongoing mucosal inflammatory reaction may contribute to the persistence of enteric neuropathy.

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Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (NHMRC) grant 400020, a University of Melbourne visiting scholar award and a Fellowship of the Fundação de Amparo à Pesquisa do Estado de São Paulo, number 2008/05718-9 (to PC) and G8 Fellowship to MB. We thank Dr. Trung Nguyen for statistical analysis. Histology facilities were provided by the Australian Phenomics Network Histopathology and Organ Pathology Node.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Melbourne, Victoria, 3010, Australia

    Louise Pontell, Patricia Castelucci, Mária Bagyánszki, Tanja Jovic, Michelle Thacker, Romke Bron & John B. Furness

  2. Department of Anatomy, University of São Paulo, São Paulo, Brazil

    Patricia Castelucci

  3. Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, 6726, Hungary

    Mária Bagyánszki

  4. Department of Physiology, University of Melbourne, Parkville, Melbourne, Victoria, 3010, Australia

    Kulmira Nurgali

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  1. Louise Pontell
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  2. Patricia Castelucci
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Correspondence to John B. Furness.

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Pontell, L., Castelucci, P., Bagyánszki, M. et al. Structural changes in the epithelium of the small intestine and immune cell infiltration of enteric ganglia following acute mucosal damage and local inflammation. Virchows Arch 455, 55–65 (2009). https://doi.org/10.1007/s00428-009-0795-x

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  • DOI: https://doi.org/10.1007/s00428-009-0795-x

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