IV. Pathophysiology of GI motility related to interstitial cells of Cajal (original) (raw)

Role of Interstitial Cells of Cajal in Motility Disorders of the Bowel

The American Journal of Gastroenterology, 2003

OBJECTIVE: Idiopathic intestinal pseudo-obstruction is characterized by the failure of the intestinal tract to propel its contents appropriately. This leads to signs and symptoms of bowel obstruction and, in the absence of an associated systemic disorder or the administration of drugs known to result in bowel dysmotility, is termed chronic idiopathic intestinal pseudo-obstruction (CIIP). Histopathologically, patients with CIIP can be characterized as having either myopathic or neuropathic forms, but the large majority of patients do not show any specific histological changes. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the bowel and have been implicated in the pathogenesis of CIIP. The aim of this study was to compare the number and distribution patterns of c-kitϩ ICC in CIIP in patients with mechanical bowel obstruction, other bowel motility disorders, and normal controls. METHODS: Six patients with CIIP, six age-matched normal controls, nine patients with mechanical bowel obstruction, and 18 patients with other motility disorders (non-CIIP), including 10 with secondary intestinal pseudo-obstruction, were studied. Toluidine blue, Masson's trichrome, and S-100 immunostaining were performed in all subjects. The ICC were identified by an indirect immunoperoxidase method using a polyclonal c-kit antibody. RESULTS: All six patients with CIIP showed total absence of c-kitϩ ICC. A subject with neonatal meconium ileus in the non-CIIP group showed patchy areas devoid of c-kitϩ ICC amid normal areas. The c-kitϩ ICC had a normal number and distribution pattern in all patients with mechanical obstruction and in the remaining 17 non-CIIP subjects. CONCLUSIONS: It seems that CIIP is characterized by a total loss of c-kitϩ ICC. ICC may play an important role in the etiopathogenesis of CIIP and transient neonatal meconium syndrome, and staining for c-kit receptor may be very useful in the evaluation of motility disorders of the bowel.

Development of interstitial cells of Cajal in a full-term infant without an enteric nervous system

Gastroenterology, 2001

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.

Interstitial cells of Cajal, The maestro in health and disease

Interstitial cells of Cajal (ICC) are important players in the symphony of gut motility. They have a very significant physiological role orchestrating the normal peristaltic activity of the digestive system. They are the pacemaker cells in gastrointestinal (GI) muscles. Absence, reduction in number or altered integrity of the ICC network may have a dramatic effect on GI system motility. More understanding of ICC physiology will foster advances in physiology of gut motility which will help in a future breakthrough in the pharmacological interventions to restore normal motor function of GI tract. This mini review describes what is known about the physiologic function and role of ICCs in GI system motility and in a variety of GI system motility disorders.

Morphology of the interstitial cells of Cajal of the human ileum from foetal to neonatal life

Journal of Cellular and Molecular Medicine, 2007

The so-called interstitial cells of Cajal myenteric plexus (ICC-MP), interstitial cells of Cajal intramuscular (ICC-IM) and interstitial cells of Cajal deep muscular plexus (ICC-DMP) are the three types of ICC endowed within the intestinal muscle coat where they play different roles in gut motility. Studies on ICC ontogenesis showed ICC-MP in the human ileum by 7-9 weeks while information on ICC-IM and ICC-DMP in foetuses and newborns are not exhaustive. Functional recordings in the fasting state of prematurely born babies aged 28-37 weeks showed immature ileal motility. To gain more information on the time of appearance of the three ICC types in the human ileum and on the steps of the acquisition of mature features, we studied by c-kit immunohistochemistry foetuses aged 17-27 weeks and newborns aged 36-41 weeks. In parallel, the maturative steps of enteric plexuses and muscle layers were immunohistochemically examined by using anti-neuron specific enolase (NSE), anti-S-100 and anti-␣ smooth muscle actin (␣SMA) antibodies. The appearance and differentiation of all the ICC types were seen to occur in concomitance with those of the related nerve plexuses and muscle layers. ICC-MP appeared first, ICC-IM and ICC-DMP later and their differentiation was incomplete at birth. In conclusion, the ICC-MP, the intestinal pacemaker cells, in spite of absence of food intake, are already present during the foetal life and the ICC-IM appear by pre-term life, thus ensuring neurotransmission. The ICC-DMP and their related nerve plexus and smooth muscle cells, i.e. the intestinal stretch receptor, begin to differentiate at birth. These findings might help in predicting neonatal ileal motor behaviour and in interpreting the role of ICC abnormalities in the pathophysiology of intestinal motile disorders of neonates and young children.

Regional and transmural density of interstitial cells of Cajal in human colon and rectum

American Journal of Physiology-Gastrointestinal and Liver Physiology, 1998

The interstitial cells of Cajal (ICC) are thought to play an important role in the control of gut motility. The regional and transmural pattern of distribution of ICC in the normal human colon and rectum was evaluated with immunohistochemistry using an anti-c- kit antibody. The transmural distribution of ICC was constant throughout the whole colon, the density of ICC was significantly greater at the myenteric plexus than at either the longitudinal or circular muscle layers, and in the rectum the transmural distribution was more even. Regionally, at the myenteric plexus, the transverse colon had a significantly greater density of ICC compared with the right colon ( P = 0.038), left colon ( P = 0.006), and rectum ( P = 0.008). The pattern of distribution of ICC identified in this study is consistent with the proposed roles of ICC as colorectal pacemakers, intermediaries of the neural control of muscle activity, and coordinators of colorectal muscle activity. The highest density of ICC...

Delayed development of interstitial cells of Cajal in the ileum of a human case of gastroschisis

Journal of Cellular and Molecular Medicine, 2008

The Interstitial Cells of Cajal (ICC) are responsible for rhythmic electrical activity. A paralytic ileus is present in gastroschisis (GS), a malformation due to a defective closure of the abdominal wall through which part of the intestine herniates during pregnancy. In experimental GS, ICC morphological immaturity was shown in the rat foetus at-term but it could not be demonstrated whether differentiation is accomplished post-natally. For this purpose we morphologically investigated ICC, as well as enteric neurons and smooth muscle cells, in a case of human GS at birth and 1 month later when peristaltic activity had initiated. A 36 weeks gestation female was born by c/section with prenatal diagnosis of GS and possible volvulus of the herniated intestine. At birth, the necrotic intestine was resected and both ileostomy and colostomy were performed. The intestine continuity was restored after 4 weeks. Intestinal specimens, taken during both operations at the level of the proximal stoma, were immunostained with c-kit, neuron-specific-enolase and ␣-smooth-muscle-actin antibodies and some processed for electron microscopy. ICC were present at the myenteric plexus only. At birth, these cells were rare and ultrastructurally immature; 1 month later, when partial enteral feeding was tolerated, they formed rows or groups and many of them were ultrastructurally differentiated. Neurons and smooth muscle cells, immature at birth, had developed after 1 month. Therefore, ICC differentiation, as well as that of neurons and smooth muscle cells, is delayed at birth and this might explain the paralytic ileus in GS. One month later, differentiation quickly proceeded at all cellular levels paralleling the increasing tolerance of enteral nutrition.