Digestive Diseases and Sciences, Vol. 30, No. 12 (December 1985 Supplement), pp, 36S-37S

Colonic Glycoproteins in Cotton-Top Tamarin

Relationship to Chronic Colitis

DANIEL K. PODOLSKY

I wanted to take a few moments to describe some biochemical studies which were carried out in con- junction with the histologic characterization of colitis in the cotton-top tamarin described earlier today by Dr. Madara. Our interest was stimulated by the recent finding of characteristic alterations in mucin glycoproteins in patients with ulcerative colitis. In these earlier studies, mucin isolated from colonic tissue of patients with ulcerative colitis demonstrated a selective absence of one mucin component (designated species IV) among the six distinct mucin species (I-VI) isolated from normal human colon. In contrast, colonic mucin from a wide variety of other inflammatory disease states (eg, Crohn's colitis, infectious colitis) was found to have a normal mixture of mucin species (1, 2).

These findings provided one focus for biochemi- cal comparison between human and tamarin colitis. Accordingly, colonic mucin glycoproteins were ex- amined in rectal mucosal biopsies from cotton-top tamarins (Saguinus oedipus; N = 18) as well as a variety of other primates(Macaca mulatta, N = 2; Macaca fascicularis, N = 2; Aotus trivirgatus, N = 2; Saimiri sciureus, N = 2). Mucin glycoproteins were isolated by Sepharose 4B chromatography after solubilization and radiolabeling by sequential treatment with sodium metaperiodate, galactose oxidase, and sodium borotritide (2). Heterogeneity of mucin glycoproteins was assessed by DEAE- cellulose chromatography. These studies demon- strated the presence of at least five labeled mucin components in monkey rectal mucosa in contrast to

Address for correspondence and reprint requests: Daniel K. Podolsky, Gastrointestinal Unit, Massachusetts General Hospi- tal, Boston, Massachusetts 02114.

This work was supported by a grant from the National Foundation for Ileitis and Colitis.

the six mucin fractions observed in the human colon. While all nonhuman primates were found to consistently lack the earliest-eluting component present in human colonic mucin, other mucin com- ponents cochromatographed with comparable frac- tions previously identified in human colonic biop- sies.

The relative proportion of each fraction was consistent throughout all primates except the cotton-top tamarin (S. oedipus). The cotton-top tamarin was found to have a markedly reduced amount of one mucin component (IV) in a manner analogous to the reduction in mucin IV previously noted in patients with ulcerative colitis. The reduc- tion in tamarin mucin IV was found both in animals with structurally defined active disease as well as in those with quiescent disease. Sequential evaluation of mucin profiles in cotton-top tamarins (N = 12) treated with sulfasalazine or placebo in a 10-week double-blind crossover study demonstrated the per- sistence of the selective reduction in species IV unrelated to disease activity. This finding resembles the results of sequential determinations of colonic mucin glycoproteins in specimens from patients.

In summary, these studies reveal a biochemical analogy between cotton-top tamarin mucin and that identified in colonic mucosal biopsies of humans with ulcerative colitis. The substantially larger amounts of mucin IV in other nonhuman primates suggest that the distinctive profile obtained consis- tently in S. oedipus is not simply a nonspecific difference distinguishing human and nonhuman pri- mates. It is of interest that the common marmoset (Callithrix jacchus), an animal also reported to develop chronic colitis, albeit without any apparent predisposition to progress to malignant degenera-

36S Digestive Diseases and Sciences, Vol. 30, No. 12 (December 1985 Supplement)

0163-2116/85/1200-036S$04.50/0 �9 1985 Plenum Publishing Corporation

COLONIC GLYCOPROTEINS IN TAMARINS

tion, was found to have an intermediate amount of primate mucin IV.

Well, that brings me to the end of this interlude. I call these data to your attention in order to indicate another point of correspondence between idiopathic chronic colonic inflammatory disease in humans and the disorder in the cotton-top tamarin which has been the focus of our attention today. However, in the absence of any disease-specific markers, I think it's important to maintain an atti- tude of caution because apparent similarities may be only superficial; as Gilbert and Sullivan appreci-

ated many years ago "Things are seldom what they seem, Skim milk masquerades as cream."

REFERENCES

1. Podolsky DK, Isselbacher KJ. Composition of human colonic mucin: Selective alterations in inflammatory bowel disease. J Clin Invest 72:142-153, 1983

2. Podolsky DK, Isselbacher KJ: Glycoprotein composition of colonic mucosa: Specific alterations in ulcerative colitis. Gastroenterology 87:991-998, 1985

3. Podolsky DK, Madara JL, King N, et al. Colonic mucin composition in primates: Selective alterations associated with spontaneous colitis in the cotton-top tamarin. Gastroenterol- ogy 88:20-25, 1984

Digestive Diseases and Sciences, Vol. 30, No. 12 (December 1985 Supplement) 37S