Identification and characterisation of mucin abnormalities in the ganglionic bowel in Hirschsprung's disease
Abstract
Hirschsprung’s disease (HD) is a congenital abnormality of unknown origin,
characterised by a lack of ganglion cells in the distal colon which results in functional
colonic obstruction. The major cause of morbidity and mortality in these children
results from an inflammatory condition called enterocolitis.
Mucins are large glycoproteins produced by intestinal cells which are a vital part of the
colonic defensive barrier to infection. Previous work has found that this barrier is
deficient in children with HD in the aganglionic colon and in the immediately adjacent
ganglionic colon and that this is related to the risk of developing enterocolitis.
This study aimed to further investigate the mucin defensive barrier in a greater region of
the ganglionic colon in HD, to establish the extent of any mucin deficiencies and
whether these were confined to a limited region close to the aganglionic colon. Mucosal
biopsies were collected at intervals along the colon at the time of corrective surgery or
colostomy closure in the controls. Organ culture with radioactive mucin precursors was
performed and the mucin produced was purified and analysed, results quantified by
DNA content in the sample. Lectin binding studies were also carried out.
Patients were found to produce lower levels of new mucins most distally, but much
higher levels five centimetres proximal when compared to controls. The rest of the
colon studied also showed changes in mucin production, with a lack of production of
gel-forming mucins and sulphated secreted mucins in Hirschsprung’s disease higher up
the colon. Lectin binding studies, which indicate the presence of existing mucins as well
as those produced during organ culture, demonstrated greater levels of binding in
patients compared to controls for wheat germ agglutinin and Maackia amurensis
agglutinin.
Authors
Speare, Ruth MarianCollections
- Theses [3706]