[Show abstract][Hide abstract] ABSTRACT: The role of interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP) in the pathophysiology of inflammation-induced abnormalities in gut motor activity is poorly understood. Therefore we applied a well-described model of inflammation (infection by Trichinella spiralis) to the mouse small intestine where the structure and function of ICC-AP are best known. Electron microscopic evaluation revealed that 1 to 3 days after infection, selective and patchy damage to the ICC processes occurred, thereby disrupting contacts between these ICC and smooth muscle cells as well as ICC and nerves, which was associated with disordered electrical activity and abnormal peristalsis. Ten to 15 days after infection, damage to ICC-AP was maximal and now involving the cell body and major processes. Marked synthetic activity and regrowth of their processes occurred from day 3 onward and recovery was completed at day 40 after infection. No changes to the network of ICC-AP were seen with c-Kit immunohistochemistry. From day 1 after infection, macrophages infiltrated the AP area, making close contact including peg-and-socket-like junctions with smooth muscle cells and ICC-AP but up to day 6 after infection without any sign of phagocytosis. By day 6 after infection, lymphocytes entered the musculature forming close contacts with ICC-AP. This was not associated with damage to ICC-AP but with proliferation of rough endoplasmic reticulum. From day 23 onward, immune cells withdrew from the musculature except macrophages, resulting in a markedly increased population of macrophages in the AP area at day 60 after infection.
American Journal Of Pathology 05/2002; 160(4):1529-40. DOI:10.1016/S0002-9440(10)62579-5 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The relationship between the development of the enteric nervous system and interstitial cells of Cajal (ICC) in the human small intestine was investigated in a full-term infant who presented with intestinal pseudo-obstruction. Immunohistochemistry revealed absence of enteric nerves and ganglia but abundant c-Kit immunoreactivity associated with Auerbach's plexus (ICC-AP). However, c-Kit immunoreactivity associated with the deep muscular plexus (ICC-DMP) and intermuscular ICC was absent. Electron microscopy showed ICC-AP with a normal ultrastructure; ICC-DMP were seen but were severely injured, suggesting degeneration. In vitro recording of intestinal muscle showed slow wave activity as well as response to cholinergic stimulation. Fluoroscopic examination of the small bowel showed a variety of motor patterns, including rhythmic, propagating contractions. In conclusion, total absence of enteric nerves was associated with absence of normal ICC-DMP. However, a normal musculature, including a network of ICC-AP, allowed for generation of rhythmic, propagating contractile activity, suggesting the presence of functional motor activity.
[Show abstract][Hide abstract] ABSTRACT: Interstitial cells of Cajal (ICC) play an important role in the control of gastrointestinal motility. We aimed to determine a potential role for ICC in the pathophysiology of inflammation-induced motor disorders.
Effects of Trichinella spiralis infection on electrical pacemaker activity, the structure of ICC associated with Auerbach's plexus, and in vivo motor patterns were studied in the mouse small intestine.
Between days 1 and 15 after infection, structural damage occurred in the network of ICC, particularly in the processes connecting ICC to each other and to smooth muscle cells. This was associated with desynchronization of electrical pacemaker activity. Abnormal slow wave activity occurred, including doubling of frequency and electrical quiescence, leading to the development of ectopic pacemaker activity in vivo. In vivo motor patterns in the small intestine changed from consistent peristaltic contractile activity in control animals to periods of quiescence alternating with both orally and aborally propagating contractile activity in the presence of inflammation. Sixty days after infection, all parameters studied had returned to normal values.
Inflammation-induced alterations in the network of ICC of the small intestine associated with Auerbach's plexus lead to disorganization of motor patterns. Because of the strong temporal correlation between damage to the ICC network, electrical uncoupling, the appearance of ectopic pacemaker activity, and the occurrence of retrograde peristalsis, it is concluded that ICC can play a major role in inflammation-induced motor disturbances.