title: Possible involvement of muscularis resident macrophages in impairment of interstitial cells of Cajal and myenteric nerve systems in rat models of TNBS-induced colitis.
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-2alpha 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.
authors.affiliation: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Tokyo 113-8657, Japan,
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Horiguchi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Fuyu
authors.initials: F
authors.lastname: Kobirumaki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamato
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ozaki
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics*; D019743:Chemokines, CXC / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D007422:Intestines / Q000294:innervation / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D009130:Muscle, Smooth / Q000294:innervation; D009197:Myenteric Plexus / Q000473:pathology*; D051381:Rats; D015854:Up-Regulation / Q000235:genetics
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; C513296:Cxcl2 protein, rat; C513294:Cxcl3 protein, rat