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

https://doi.org/10.1053/jpsu.2000.0350539Get rights and content

Abstract

Background/Purpose: Chronic intestinal pseudo-obstruction (CIP) in infants and children is a motility disorder without apparent mechanical cause. Nitric oxide (NO), an inhibitory neurotransmitter and c- kit cells, essential for the intestinal pacemaker activity, both play a key role in the intestinal motility function. In the current study, the authors investigated the distributive change in the intestinal nitric oxide synthase (NOS) and c- kit cells of patients with CIP. Methods: Tissues were obtained from 4 patients undergoing bowel resection or 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. Immunohistochemical studies were performed on paraffin-embedded tissue cross sections with neuronal NOS and inducible NOS monoclonal antibody as well as a rabbit polyclonal 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 submucosal plexus and longitudinal muscle layer, there was no change in NOS immunoreactivity. Inducible NOS immunoreactivity was not detected in the control cases. However, in tissues of CIP, almost all the epithelial cells were positively and strongly labeled for inducible NOS immunoreactivity. For c- kit cells staining, the number of c- kit—positive cells in the myenteric plexus and circular muscle layers were greatly less than that in the controls, especially in the myenteric plexus region. Conclusion: These findings suggest that sustained production of NO by an increased NOS activity and a deficiency of c-kit cells in the intestine may be related to the pathogenesis of CIP. J Pediatr Surg 35:539-544. Copyright © 2000 by W.B. Saunders Company.

Section snippets

Tissues

Tissues were obtained from 4 patients undergoing bowel resection or biopsy for CIP at laparotomy. The patients' ages ranged from 1 month to 3 months. All suffered with episodes of functional obstruction and intolerance to enteral feeding. Diagnosis of CIP was confirmed by contrast radiography, laparotomy, and histology with the exclusion of other diseases. For controls, the intestinal specimens were obtained from 4 age-matched patients undergoing intestinal resection for intestinal stricture (n

NOS immunoreactivity

Numerous NOS reactive structures were seen in the tissue sections from control patients (Fig 1A).

. Immunohistochemical localization of neuronal NOS in the external muscle layer of intestine. (A) Control section. NOS immunoreactivity is present in nerve cell bodies (arrows) of the myenteric plexus (mp) and in many nerve fibers (arrowhead) in the circular muscle layer (cm). (B) CIP section. Greatly increased intensity of NOS immunoreactivity in nerve cell bodies and nerve bundles (nb) in the

Discussion

CIP is a clinical syndrome caused by severe abnormality of gastrointestinal motility in infants and children. The etiology of CIP remains unknown. NO, a vital component of normal GI physiology, is important to GI motility. It has been well reported that NO serves as a nonadrenergic and noncholinergic inhibitory neurotransmitter in the GI tract,21 causing the relaxation of the enteric smooth musculature. Neuronal NOS is expressed in the myenteric neurons and many nerve fibers of the musculature.

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    Address reprint requests to Z.Q. Wang, MD, PhD, Department of Pediatric Surgery, Kagawa Medical University Faculty of Medicine, 1750-1, Miki, Kita-gun, Kagawa, 761-07 Japan.

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