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Possible involvement of muscularis resident macrophages in impairment of interstitial cells of Cajal and myenteric nerve systems in rat models of TNBS-induced colitis

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Abstract

Resident macrophages are distributed in the network of interstitial cells of Cajal (ICC) and the myenteric nerve within the myenteric plexus. We evaluated changes in chemoattractant protein mRNA expression in macrophages and neutrophils, the ICC, nerve and macrophages in the myenteric plexus of model rats with TNBS-induced colitis. Chemoattractant proteins, MCP-1, GRO, MIP-2 and CINC-2α were upregulated in the colonic muscle layer after inflammation. Leukocyte infiltration and MPO activity were increased in the muscle layer. Electron microscopy indicated an irregular contour of the myenteric ganglia into which numerous macrophages had penetrated. Macrophages were also distributed near the ICC in the inflamed myenteric plexus. Immunohistochemistry showed that the ICC network and myenteric nerve system had disappeared from the inflamed region, whereas the number of resident macrophages was increased. TTX-insensitive, possibly ICC-mediated, rhythmic contractions of circular smooth muscle strips and enteric neuron-mediated TTX-sensitive peristalsis in the whole proximal colon tissue were significantly inhibited in the inflamed colon, indicating that the ICC-myenteric nerve system was dysfunctional in the inflamed muscle layer. Their accumulation around the myenteric nerve plexus and the ICC network suggests that macrophages play an important role in inducing intestinal dysmotility in gut inflammation.

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Acknowledgments

This work was supported in part by a Grant-in Aid for scientific research from the Japanese Ministry of Education, the Program for the Promotion of Basic Research Activities for Innovative Biosciences (BRAIN), and Morinaga Hoshi-kai.

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Authors and Affiliations

  1. Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo, 113-8657, Japan

    Kazuya Kinoshita, Kazuhide Horiguchi, Masahiko Fujisawa, Fuyu Kobirumaki, Masatoshi Hori & Hiroshi Ozaki

  2. International Medical Center of Japan, Toyama 1-21-1, Shinjuku-ku, Tokyo, 162-8655, Japan

    Shigeru Yamato

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  1. Kazuya Kinoshita
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  2. Kazuhide Horiguchi
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  3. Masahiko Fujisawa
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Correspondence to Masatoshi Hori.

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Kinoshita, K., Horiguchi, K., Fujisawa, M. et al. Possible involvement of muscularis resident macrophages in impairment of interstitial cells of Cajal and myenteric nerve systems in rat models of TNBS-induced colitis. Histochem Cell Biol 127, 41–53 (2007). https://doi.org/10.1007/s00418-006-0223-0

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