Possible involvement of muscularis resident macrophages in impairment of interstitial cells of Cajal and myenteric nerve systems in rat models of TNBS-induced colitis
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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DOI：
10.1007/s00418-006-0223-0
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发表时间：
2007-01-01
影响因子：
2.3
通讯作者：
Ozaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Kinoshita, Kazuya;Horiguchi, Kazuhide;Ozaki, Hiroshi
驻留巨噬细胞分布在Cajal间质细胞（ICC）和肌间神经丛内的肌间神经网络中。我们评估了TNBS诱导的结肠炎模型大鼠肌间神经丛中巨噬细胞和中性粒细胞、ICC、神经和巨噬细胞中趋化蛋白mRNA表达的变化。炎症后结肠肌层中趋化蛋白MCP-1、GRO、MIP-2和CINC-2 α上调。肌层白细胞浸润和MPO活性增加。电子显微镜检查显示肌间神经节的不规则轮廓，许多巨噬细胞已渗透其中。巨噬细胞也分布在炎症的肌间神经丛的ICC附近。免疫组化显示，ICC网络和肌间神经系统已从炎症区域消失，而驻留的巨噬细胞的数量增加。在整个近端结肠组织中，TTX不敏感的，可能是ICC介导的，环形平滑肌条的节律性收缩和肠神经元介导的TTX敏感性收缩在发炎的结肠中被显著抑制，表明ICC-肌间神经系统在发炎的肌肉层中功能障碍。它们在肌间神经丛和ICC网络周围的积累表明巨噬细胞在肠道炎症中诱导肠道运动障碍中起重要作用。
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-2 alpha 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.