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


CONCLUSIONS
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.
Wang
Z Q
ZQ
Department of Pediatric Surgery, Kagawa Medical University, Faculty of Medicine, Kita-gun, Japan.
Watanabe
Y
Y
Toki
A
A
Kohno
S
S
Hasegawa
S
S
Hamazaki
M
M
D002908:Chronic Disease; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007418:Intestinal Pseudo-Obstruction / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*
D009419:Nerve Tissue Proteins; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D019009:Proto-Oncogene Proteins c-kit