Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1995 Feb;146(2):310–316.

Influence of inflammatory bowel disease on the distribution and concentration of pancreatic secretory trypsin inhibitor within the colon.

R J Playford 1, A M Hanby 1, K Patel 1, J Calam 1
PMCID: PMC1869860  PMID: 7856742

Abstract

Gastrointestinal epithelia contain a powerful protease inhibitor called pancreatic secretory trypsin inhibitor (PSTI). Patients with inflammatory bowel disease have changes in mucus structure suggestive of increased proteolysis. We therefore examined the distribution and concentration of PSTI in the colon of normal subjects and patients with inflammatory bowel disease. In normal subjects (N = 12), mucosal levels of PSTI were approximately 200 ng/mg protein in all regions of the colon and was localized to goblet and endocrine cells. Mucosal PSTI levels in the (affected) left side of the colon of patients with active (N = 12) or quiescent (N = 10) ulcerative colitis were reduced (approximately 80% of control in descending colon, 55% of control in sigmoid colon, and 50% of control in rectum, all P < 0.01), whereas levels in the (unaffected) right side of the colon were normal. PSTI levels were also reduced to approximately 65% of control in colonic tissue affected by Crohn's disease (N = 6, P = 0.01) and immunostaining showed PSTI positivity within the ulcer-associated cell lineage. As the mucous layer is important in preserving mucosal integrity, our finding of prolonged reduction in mucosal PSTI levels after an episode of ulcerative colitis probably represents a long-term reduction in a mucosal defense mechanisms that could lead to increased susceptibility to episodes of inflammation.

Full text

PDF
310

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bohe H., Bohe M., Jönsson P., Lindström C., Ohlsson K. Quantification of pancreatic secretory trypsin inhibitor in colonic carcinoma and normal adjacent colonic mucosa. J Clin Pathol. 1992 Dec;45(12):1066–1069. doi: 10.1136/jcp.45.12.1066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clamp J. R., Fraser G., Read A. E. Study of the carbohydrate content of mucus glycoproteins from normal and diseased colons. Clin Sci (Lond) 1981 Aug;61(2):229–234. doi: 10.1042/cs0610229. [DOI] [PubMed] [Google Scholar]
  3. Corfield A. P., Williams A. J., Clamp J. R., Wagner S. A., Mountford R. A. Degradation by bacterial enzymes of colonic mucus from normal subjects and patients with inflammatory bowel disease: the role of sialic acid metabolism and the detection of a novel O-acetylsialic acid esterase. Clin Sci (Lond) 1988 Jan;74(1):71–78. doi: 10.1042/cs0740071. [DOI] [PubMed] [Google Scholar]
  4. Eastwood G. L., Trier J. S. Epithelial cell renewal in cultured rectal biopsies in ulcerative colitis. Gastroenterology. 1973 Mar;64(3):383–390. [PubMed] [Google Scholar]
  5. Freeman T. C., Curry B. J., Calam J., Woodburn J. R. Pancreatic secretory trypsin inhibitor stimulates the growth of rat pancreatic carcinoma cells. Gastroenterology. 1990 Nov;99(5):1414–1420. doi: 10.1016/0016-5085(90)91170-b. [DOI] [PubMed] [Google Scholar]
  6. Freeman T. C., Playford R. J., Quinn C., Beardshall K., Poulter L., Young J., Calam J. Pancreatic secretory trypsin inhibitor in gastrointestinal mucosa and gastric juice. Gut. 1990 Nov;31(11):1318–1323. doi: 10.1136/gut.31.11.1318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fukayama M., Hayashi Y., Koike M., Ogawa M., Kosaki G. Immunohistochemical localization of pancreatic secretory trypsin inhibitor in fetal and adult pancreatic and extrapancreatic tissues. J Histochem Cytochem. 1986 Feb;34(2):227–235. doi: 10.1177/34.2.3511141. [DOI] [PubMed] [Google Scholar]
  8. Fukuoka S., Fushiki T., Kitagawa Y., Sugimoto E., Iwai K. Competition of a growth stimulating-/cholecystokinin (CCK) releasing-peptide (monitor peptide) with epidermal growth factor for binding to 3T3 fibroblasts. Biochem Biophys Res Commun. 1987 Jun 15;145(2):646–650. doi: 10.1016/0006-291x(87)91013-8. [DOI] [PubMed] [Google Scholar]
  9. Guesdon J. L., Ternynck T., Avrameas S. The use of avidin-biotin interaction in immunoenzymatic techniques. J Histochem Cytochem. 1979 Aug;27(8):1131–1139. doi: 10.1177/27.8.90074. [DOI] [PubMed] [Google Scholar]
  10. Hanby A. M., Wright N. A. The ulcer-associated cell lineage: the gastrointestinal repair kit? J Pathol. 1993 Sep;171(1):3–4. doi: 10.1002/path.1711710103. [DOI] [PubMed] [Google Scholar]
  11. Horii A., Kobayashi T., Tomita N., Yamamoto T., Fukushige S., Murotsu T., Ogawa M., Mori T., Matsubara K. Primary structure of human pancreatic secretory trypsin inhibitor (PSTI) gene. Biochem Biophys Res Commun. 1987 Dec 16;149(2):635–641. doi: 10.1016/0006-291x(87)90415-3. [DOI] [PubMed] [Google Scholar]
  12. Hunt L. T., Barker W. C., Dayhoff M. O. Epidermal growth factor: internal duplication and probable relationship to pancreatic secretory trypsin inhibitor. Biochem Biophys Res Commun. 1974 Oct 8;60(3):1020–1028. doi: 10.1016/0006-291x(74)90415-x. [DOI] [PubMed] [Google Scholar]
  13. Hutton D. A., Pearson J. P., Allen A., Foster S. N. Mucolysis of the colonic mucus barrier by faecal proteinases: inhibition by interacting polyacrylate. Clin Sci (Lond) 1990 Mar;78(3):265–271. doi: 10.1042/cs0780265. [DOI] [PubMed] [Google Scholar]
  14. MacDermott R. P., Donaldson R. M., Jr, Trier J. S. Glycoprotein synthesis and secretion by mucosal biopsies of rabbit colon and human rectum. J Clin Invest. 1974 Sep;54(3):545–554. doi: 10.1172/JCI107791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McCormick D. A., Horton L. W., Mee A. S. Mucin depletion in inflammatory bowel disease. J Clin Pathol. 1990 Feb;43(2):143–146. doi: 10.1136/jcp.43.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ogawa M., Tsushima T., Ohba Y., Ogawa N., Tanaka S., Ishida M., Mori T. Stimulation of DNA synthesis in human fibroblasts by human pancreatic secretory trypsin inhibitor. Res Commun Chem Pathol Pharmacol. 1985 Oct;50(1):155–158. [PubMed] [Google Scholar]
  17. Playford R. J., Batten J. J., Freeman T. C., Beardshall K., Vesey D. A., Fenn G. C., Baron J. H., Calam J. Gastric output of pancreatic secretory trypsin inhibitor is increased by misoprostol. Gut. 1991 Nov;32(11):1396–1400. doi: 10.1136/gut.32.11.1396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Playford R. J., Hanby A. M., Quinn C., Calam J. Influence of inflammation and atrophy on pancreatic secretory trypsin inhibitor levels within the gastric mucosa. Gastroenterology. 1994 Mar;106(3):735–741. doi: 10.1016/0016-5085(94)90709-9. [DOI] [PubMed] [Google Scholar]
  19. Podolsky D. K., Isselbacher K. J. Glycoprotein composition of colonic mucosa. Specific alterations in ulcerative colitis. Gastroenterology. 1984 Nov;87(5):991–998. [PubMed] [Google Scholar]
  20. Pullan R. D., Thomas G. A., Rhodes M., Newcombe R. G., Williams G. T., Allen A., Rhodes J. Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis. Gut. 1994 Mar;35(3):353–359. doi: 10.1136/gut.35.3.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Raouf A., Parker N., Iddon D., Ryder S., Langdon-Brown B., Milton J. D., Walker R., Rhodes J. M. Ion exchange chromatography of purified colonic mucus glycoproteins in inflammatory bowel disease: absence of a selective subclass defect. Gut. 1991 Oct;32(10):1139–1145. doi: 10.1136/gut.32.10.1139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schacterle G. R., Pollack R. L. A simplified method for the quantitative assay of small amounts of protein in biologic material. Anal Biochem. 1973 Feb;51(2):654–655. doi: 10.1016/0003-2697(73)90523-x. [DOI] [PubMed] [Google Scholar]
  23. Scheving L. A. Primary amino acid sequence similarity between human epidermal growth factor-urogastrone, human pancreatic secretory trypsin inhibitor, and members of porcine secretin family. Arch Biochem Biophys. 1983 Oct 15;226(2):411–413. doi: 10.1016/0003-9861(83)90309-0. [DOI] [PubMed] [Google Scholar]
  24. Sellers L. A., Allen A., Morris E. R., Ross-Murphy S. B. Mucus glycoprotein gels. Role of glycoprotein polymeric structure and carbohydrate side-chains in gel-formation. Carbohydr Res. 1988 Jul 15;178:93–110. doi: 10.1016/0008-6215(88)80104-6. [DOI] [PubMed] [Google Scholar]
  25. Wright N. A., Pike C., Elia G. Induction of a novel epidermal growth factor-secreting cell lineage by mucosal ulceration in human gastrointestinal stem cells. Nature. 1990 Jan 4;343(6253):82–85. doi: 10.1038/343082a0. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES