CHILDREN WITH HIRSCHSPRUNGS-DISEASE HAVE AN ABNORMAL COLONIC MUCUS DEFENSIVE BARRIER INDEPENDENT OF THE BOWEL INNERVATION STATUS

The mucus gel layer in the colon plays an important role in the defens ive mechanisms against pathogenic organisms. Mucin glycoproteins or mu cins are the major component of this gel. We studied the mucins in pat ients who had Hirschsprung's disease (HD) by colonic mucosal organ cul ture with radioactive mucin precursors [35S]-sulphate and [3H]-glucosa mine. The secreted and cellular mucus fractions were collected after 2 4-hour incubation, and mucins were purified by gel filtration. The rat io of incorporation of the precursors and their turnover were quantifi ed. Purified mucins were tested against wheat germ agglutinin for tota l mucin turnover. We used nine aganglionic bowel samples, 10 ganglioni c bowel samples from HD patients, and 13 age-matched normal controls. There were no significant differences in the three groups in ratio of incorporation. The turnover with both radioactive precursors was reduc ed in both aganglionic and ganglionic bowel of HD, these differences w ere significant in [35S]-sulphate incorporation in the cellular fracti on, ganglionic bowel being most affected. Total mucin turnover, as ass essed by reactivity with wheat germ aggultinin, was reduced in both HD groups, being significant in the cellular fraction, aganglionic bowel being the most affected. These results signify an abnormal mucus defe nsive barrier in the colon of HD patients, even in the ganglionic bowe l, which is thought to be normal and is retained at the definitive pul l-through operation. This abnormality may be an etiological factor in the pathogenesis of enterocolitis of HD. Copyright (C) 1997 by W.B. Sa unders Company.