Involvement of endogenous nitric oxide and c-kit-expressing cells in chronic intestinal pseudo-obstruction

Background/Purpose: Chronic intestinal pseudo-obstruction (CIP) in infants and children is a motility disorder without apparent mechanical cause. Nitr ic oxide (NO), an inhibitory neurotransmitter and c-kit cells, essential fo r the intestinal pacemaker activity, both play a key role in the intestinal motility function. In the current study, the authors investigated the dist ributive change in the intestinal nitric oxide synthase (NOS) and c-kit cel ls of patients with CIP. Methods: Tissues were obtained from 4 patients undergoing bowel resection o r biopsy for CIP at laparotomy. For controls, the intestinal specimens were obtained from 4 age-matched cases of intestinal stricture, intussusception , and autopsy with no evidence of gastrointestinal disease. Immunohistochem ical studies were performed on paraffin-embedded tissue cross sections with neuronal NOS and inducible NOS monoclonal antibody as well as a rabbit pol yclonal antibody against the human c-kit receptor. Results: Under immunohistochemical staining, a greatly increased density of neuronal NOS immunoreactivity and an evidently increased number of intense NOS immunoreactive nerve fibers were observed in the myenteric plexus and circular muscle layers compared with the control sections. In the submucosa l plexus and longitudinal muscle layer, there was no change in NOS immunore activity. Inducible NOS immunoreactivity was not detected in the control ca ses. However, in tissues of CIP, almost all the epithelial cells were posit ively and strongly labeled for inducible NOS immunoreactivity. For c-kit ce lls staining, the number of c-kit-positive cells in the myenteric plexus an d circular muscle layers were greatly less than that in the controls, espec ially in the myenteric plexus region. Conclusion: These findings suggest that sustained production of NO by an in creased NOS activity and a deficiency of c-kit cells in the intestine may b e related to the pathogenesis of CIP. Copyright (C) 2000 by W.B. Saunders C ompany.