Motility disorder in experimentally obstructed intestine: relationship between muscularis inflammation and disruption of the ICC network

Abstract

We designed a model of small intestinal obstruction in rats to investigate changes in intestinal contractility associated with the immunologically activated components in the tunica muscularis. Although histochemical study did not reveal any typical inflammatory signs such as leucocyte infiltration in the distended intestinal regions of model rats 2-3 weeks after surgical induction of intestinal obstruction, the number of ED2-positive macrophages appeared to be increased in the tunica muscularis. Expression of tumour necrosis factor (TNF)-alpha mRNA was also significantly increased, and the level of CD14 was also increased significantly in the tunica muscularis. Functional studies of distended intestinal muscle segments showed a marked decrease in absolute force stimulated by a cholinergic agent. In addition, the number of spontaneous rhythmic contractions was also reduced in the distended intestinal regions of the obstructed intestine, and this decrease was associated with a reduction in the number of interstitial cells of Cajal (ICC), as revealed by Kit-like immunoreactivity. These results suggest that, under the pro-inflammatory conditions of the tunica muscularis associated with intestinal obstruction, the release of bioactive substances, possibly from activated resident macrophages, may affect smooth muscle contractility. Furthermore, under these conditions, both the number and the function of neighbouring ICC may also be affected.