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Immunolocalization and Expression of Kallistatin and Tissue Kallikrein in Human Inflammatory Bowel Disease

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Abstract

The distribution of tissue kallikrein (TK) and its plasma inhibitor, kallistatin in plasma and intestinal tissue, was studied in patients with active ulcerative colitis (UC) and Crohn's disease (CD). TK was localized to goblet cells and kallistatin to epithelial cells of normal human intestine. Both proteins are visualized in macrophages inside granulomas in CD as well as in plasmocytes in both CD and UC. Intestinal tissue kallikrein (ITK) and kallistatin are significantly decreased in inflamed intestine compared to noninflammatory controls. TK mRNA is significantly decreased in intestinal biopsy samples from active UC patients compared with inactive patients or controls. Immunoreactive TK is present in plasma in very low concentrations in patients and did not differ in normal subjects. Plasma kallistatin was significantly decreased in patients with active disease compared to normal controls. Our data suggest that release of TK during inflammation plays a role in inflammatory bowel disease.

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References

  1. Burch RM, Connor JR, Tiffany CW: The kallikrein-kininogen-kinin system in chronic inflammation. Agents Actions 27:258-260, 1989

    Google Scholar 

  2. DeLa Cadena RA, Laskin KJ, Pixley RA, Sartor RB, Schwab JH, Back N, Bedi GS, Fisher RS, Colman RW: Role of kallikrein-kinin system in pathogenesis of bacterial cell wall-induced inflammation. Am J Physiol 260:G213-G219, 1991

    Google Scholar 

  3. DeLa Cadena RA, Stadnicki A, Uknis AB, Sartor RB, Kettner CA, Adam A, Colman RW: Inhibition of plasma kallikrein prevents peptidoglycan-induced arthritis in the Lewis rat. FASEB J 9:446-452, 1995

    Google Scholar 

  4. Sartor RB, DeLa Cadena RA, Green KD, Stadnicki A, Davis SW, Schwab JH, Adam AA, Raymond P, Colman RW: Selective kallikrein-kinin system activation in inbred rats differentially susceptible to granulomatous enterocolitis. Gastroenterology 110:1467-1481, 1996

    Google Scholar 

  5. Stadnicki A, Sartor RB, Janardham R, Stadnicka I, Adam A, Blais C, Colman RW: Kallikrein-kininogen system activation and bradykinin (B2) receptors in indomethacin-induced enterocolitis in genetically susceptible Lewis rats. Gut 43:365-374, 1998

    Google Scholar 

  6. Stadnicki A, DeLa Cadena RA, Sartor RB, Bender D, Kettner CA, Rath HC, Adam A, Colman RW: Selective plasma kallikrein inhibitor attenuates acute intestinal inflammation in Lewis rat. Dig Dis Sci 41:912-920, 1996

    Google Scholar 

  7. Stadnicki A, Sartor RB, Janardham R, Majluf-Cruz A, Kettner C, Adam AA, Colman RW: Specific inhibition of plasma kallikrein modulates chronic granulomatous intestinal and systemic inflammation in genetically susceptible rats. FASEB J 12:325-333, 1998

    Google Scholar 

  8. Stadnicki A, Gonciarz M, Niewiarowski TJ, Hartleb J, Rudnicki M, Merrell NB, DeLa Cadena RA, Colman RW: Activation of plasma contact and coagulation systems and neutrophils in the active phase of ulcerative colitis. Dig Dis Sci 42:2356-2366, 1997

    Google Scholar 

  9. Blais C Jr., Couture R, Drapeau G, Colman RW, Adam AA: Involvement of endogenous kinins in the pathogenesis of peptidoglycan-induced arthritis in the Lewis rat. Arthritis Rheum 40:1327-1333, 1997

    Google Scholar 

  10. Wolf WC, Harley RA, Sluce D, Chao L, Chao J: Cellular localization of kallistatin and tissue kallikrein in human pancreas and salivary glands. Histochem Cell Biol 110:477-484, 1998

    Google Scholar 

  11. Stadnicki A, Chao J, Stadnicka I, van To1 E, Lin KF, Sartor RB, Colman RW: Localization and secretion of tissue kallikrein in peptidoglycan-induced enterocolitis in Lewis rats. Am J Physiol 275:G854-G861, 1998

    Google Scholar 

  12. Best WR, Becktel JM, Singleton JW, Kern F Jr: Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology 70:439-444, 1976

    Google Scholar 

  13. Chen LM, Richards GP, Chao L, Chao J: Molecular cloning, purification and in situ localization of human colon kallikrein. Biochem J 307:481-486, 1995

    Google Scholar 

  14. Wang C, Chao L, Chao J: Direct gene delivery of human tissue kallikrein reduces blood pressure in spontaneously hypertensive rats. J Clin Invest 95:1710-1716, 1995

    Google Scholar 

  15. Zhou G X, Chao L, Chao J: Kallistatin: a novel human tissue kallikrein inhibitor. Purification, characterization, and reactive center sequence. J Biol Chem 267:25873-25880, 1992

    Google Scholar 

  16. Plewka A, Kaminski M, Plewka D: Ontogenesis of hepatocyte respiration processes in relation to rat liver cytochrome P450-dependent monooxygenase system. Mech Ageing Dev 105:197-207, 1998

    Google Scholar 

  17. Baron JH, Connell AM, Lennard-Jones JE: Variation between observers in describing mucosal appearances in proctocolitis. Br Med J 1:89-92, 1964

    Google Scholar 

  18. Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate—phenol—chloroform extraction. Anal Biochem 162:156-159, 1987

    Google Scholar 

  19. Chao J, Schmaier AH, Chen L-M, Yang Z, Chao L: Kallistatin, a novel human tissue kallikrein inhibitor: levels in body fluids, blood cells, and tissues in health and disease. J Lab Clin Med 127:612-620, 1996

    Google Scholar 

  20. Devani M, Cugno M, Vecchi M, Ferrero S, Di Berardino F, Avesani EC, De Franchis R, Colman RW. Kallikrein-kinin system activation in Crohn's disease: differences in intestinal and systemic markers. Am J Gastroenterol 97:2026-2032, 2002

    Google Scholar 

  21. Werle E: Kallikrein, kallidin and related substances. In Polypeptides Which Affect Smooth Muscles and Blood Vessels. M. Schachter (ed). Oxford, Pergamon Press, 1960

    Google Scholar 

  22. Fujimori H, Levison PR, Schachter M: Purification and partial characterization of cat colon and submandibular gland kallikreins. Adv Exp Med Biol 198 (Pt A):211-218, 1986

    Google Scholar 

  23. Clements J, Mukhtar A, Ehrlich A, Fuller P: A re-evaluation of the tissue-specific pattern of expression of the rat kallikrein gene family. Agents Actions Suppl 38:34-41, 1992

    Google Scholar 

  24. Figueroa CD, MacIver AG, Bhoola KD: Identification of a tissue kallikrein in human polymorphonuclear leucocytes. Br J Haematol 72:321-328, 1989

    Google Scholar 

  25. Xiong W, Tang CQ, Zhou GX, Chao L, Chao J: In vivo catabolism of human kallikrein-binding protein and its complex with tissue kallikrein. J Lab Clin Med 119:514-521, 1992

    Google Scholar 

  26. Fasth S, Hulten L: The effect of bradykinin on intestinal motility and blood flow. Acta Chir Scand 139:699-705, 1973

    Google Scholar 

  27. Podolsky DK, Fournier DA: Alterations in mucosal content of colonic glycoconjugates in inflammatory bowel disease defined by monoclonal antibodies. Gastroenterology 95:379-387, 1988

    Google Scholar 

  28. Zeitlin IJ, Smith AN: Mobilization of tissue kallikrein in inflammatory disease of the colon. Gut 14:133-138, 1973

    Google Scholar 

  29. Stanley CM, Phillips TE: Bradykinin modulates mucin secretion but not synthesis from an intestinal goblet cell line. Agents Actions 42:141-145, 1994

    Google Scholar 

  30. Wolf WC, Harley RA, Sluce D, Chao L, Chao J: Localization and expression of tissue kallikrein and kallistatin in human blood vessels. J Histochem Cytochem 47:221-228, 1999

    Google Scholar 

  31. Cuthbert AW, Kirkland SC, Mac Vinish LJ: Kinin effects on ion transport in monolayers of HCA-7 cells, a line from a human colonic adenocarcinoma. Br J Pharmacol 86:3-5, 1985

    Google Scholar 

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Stadnicki, A., Mazurek, U., Gonciarz, M. et al. Immunolocalization and Expression of Kallistatin and Tissue Kallikrein in Human Inflammatory Bowel Disease. Dig Dis Sci 48, 615–623 (2003). https://doi.org/10.1023/A:1022569623350

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  • DOI: https://doi.org/10.1023/A:1022569623350

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