Zq. Wang et al., Involvement of endogenous nitric oxide and c-kit-expressing cells in chronic intestinal pseudo-obstruction, J PED SURG, 35(4), 2000, pp. 539-544
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.