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Selective plasma kallikrein inhibitor attenuates acute intestinal inflammation in lewis rat

  • Intestinal Disorders, Inflammatory Bowel Disease, Immunology, And Microbiology
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Abstract

A specific plasma kallikrein inhibitor, Bz-Pro-Phe-boroArg (P8720), was used to define the relationship between the kallikrein-kinin (K-K) system and acute intestinal inflammation induced by bacterial peptidoglycan-polysaccharide (PG-APS) in Lewis rats. Group I received human serum albumin (HSA) intramurally in the intestine and was treated with HSA. Group II received PG-APS and was treated with P8720. Group III received PG-APS and was treated with HSA. P8720 attenuated the decrease of high-molecular-weight kininogen and factor XI activity (group II vs group III,P<0.01). P8720 therapy significantly but modestly decreased acute intestinal inflammation measured by gross gut score (P<0.01) and more dramatically reduced the tissue myeloperoxidase activity (P<0.05), a measure of granulocyte recruitment, in group II compared with group III. We conclude that the K-K system is directly involved in the pathogenesis of the acute phase of experimental acute inflammation. A specific inhibitor may modulate inflammatory bowel disease.

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References

  1. Sartor RB: Current concepts of the etiology and pathogenesis of ulcerative colitis and Crohn's disease. Gastroenterol Clin North Am 24:475–508, 1995

    Google Scholar 

  2. Schwab JH: Phlogistic properties of peptidoglycan-polysaccharide polymers from cell walls of pathogenic and normal-flora bacteria which colonize humans. Infect Immun 61:4535–4539, 1993

    Google Scholar 

  3. McCall R, Haskill S, Zimmermann E, Lund P, Thompson R, Sartor R: Tissue interleukin 1 and interleukin-1 receptor antagonist expression in enterocolitis in resistant and susceptible rats. Gastroenterology 106:960–972, 1994

    Google Scholar 

  4. Yamada T, Sartor RB, Marshall S, Specian RD, Grisham MB: Mucosal injury and inflammation in a model of chronic granulomatous colitis. Gastroenterology 105:399–409, 1993

    Google Scholar 

  5. 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 

  6. Sartor RB: Cytokines in intestinal inflammation: Pathophysiological and clinical considerations. Gastroenterology 106:533–539, 1994

    Google Scholar 

  7. DeLa Cadena RA, Adam A, Sartor RB, Raymond B, Legris F, Colman RW: The kallikrein-kinin system in experimental granulomatous enterocolitis. Thromb Haemost 69:871, 1993 (abstract)

    Google Scholar 

  8. Scott CF, Silver LD, Schapira M, Colman RW: Cleavage of human high molecular weight kininogen markedly enhances its coagulant activity. Evidence that this molecule exists as a procofactor. J Clin Invest 73:954–962, 1984

    Google Scholar 

  9. Kaplan A, Silverberg M: The coagulation-kinin pathway of human plasma. Blood 70:1–15, 1987

    Google Scholar 

  10. Kaplan AP, Kay AB, Austen KF: A prealbumin activator of prekallikrein. 3. Appearance of chemotactic activity for human neutrophils by the conversion of human prekallikrein to kallikrein. J Exp Med 135:81–97, 1972

    Google Scholar 

  11. Wachtfogel YT, Kucich U, James HL, Scott CF, Schapira M, Zimmerman M, Cohen AB, Colman RW: Human plasma kallikrein releases neutrophil elastase during blood coagulation. J Clin Invest 72:1672–1677, 1983

    Google Scholar 

  12. Zimmerli W, Huber I, Bouma B, Lammle B: Purified human plasma kallikrein does not stimulate but primes neutrophils for superoxide production. Thromb Haemost 62:1121–1125, 1989

    Google Scholar 

  13. DeLa Cadena RA, Wachtfogel YT, Colman RW: Contact activation pathway: Inflammation and coagulation.In Hemostasis and Thrombosis: Basic Principles and Clinical Practice. RW Colman, J Hirsh, VJ Marder, EW Salzman (eds). Philadelphia, Lippincott, 1994, p219

    Google Scholar 

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

    Google Scholar 

  15. Kettner C, Mersinger L, Knabb R: The selective inhibition of thrombin by peptides of boroarginine. J Biol Chem 265:18289–18297, 1990

    Google Scholar 

  16. Grisham M, Benoit J, Granger D: Assessment of leukocyte involvement during ischemia and reperfusion of intestine. Methods Enzymol 186:729–742, 1990

    Google Scholar 

  17. DeLa Cadena RA, Scott CF, Colman RW: Evaluation of a microassay for human plasma prekallikrein. J Lab Clin Med 109:601–607, 1987

    Google Scholar 

  18. Scott CF, Colman RW: A simple and accurate microplate assay for the determination of factor XI in plasma. J Lab Clin Med 111:708–714, 1988

    Google Scholar 

  19. Proctor RR, Rapaport SI: The partial thromboplastin time with kaolin: a simple screening test for first stage plasma clotting factor deficiencies. Am J Clin Pathol 36:212–219, 1961

    Google Scholar 

  20. Colman RW, Bagdasarian A, Talamo RC, Scott CF, Seavey M, Guimaraes JA, Pierce JV, Kaplan AP: Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways. J Clin Invest 56:1650–1662, 1975

    Google Scholar 

  21. Scott CF: Determination of antithrombin III (ATIII) using the Coatest Antithrombin Kit and a microplate system. Ann NY Acad Sci 485:443–444, 1985

    Google Scholar 

  22. Bergmeyer HU, Scheibe P, Wahlefeld AW: Optimization of methods for aspartate aminotransferase and alanine aminotransferase. Clin Chem 24:58–73, 1978

    Google Scholar 

  23. Page JD, Colman RW: Localization of distinct functional domains on prekallikrein for interaction with both high molecular weight kininogen and activated factor XII in a 28-kDa fragment (amino acids 141–371). J Biol Chem 266:8143–8148, 1991

    Google Scholar 

  24. Morrison D, Cochrane C: Direct evidence for Hageman factor (factor XII) activation by bacterial lipopolysaccharides (endotoxins). J Exp Med 140:797–811, 1974

    Google Scholar 

  25. Murphy EA: Biostatistics in Medicine. Baltimore, The Johns Hopkins Press, 1982

    Google Scholar 

  26. Mason JW, Kleeberg U, Dolan P, Colman RW: Plasma kallikrein and Hageman factor in gram-negative bacteremia. Ann Intern Med 73:545–551, 1970

    Google Scholar 

  27. Colman RW, Edelman R, Scott CF, Gilman RH: Plasma kallikrein activation and inhibition during typhoid fever. J Clin Invest 61:287–296, 1978

    Google Scholar 

  28. DeLa Cadena RA, Suffredini AF, Page JD, Pixley RA, Kaufman N, Parrillo JE, Colman RW: Activation of the kallikreinkinin system after endotoxin administration to normal human volunteers. Blood 81:3313–3317, 1993

    Google Scholar 

  29. Colman RW, Flores DN, DeLa Cadena RA, Scott CF, Cousens L, Barr PJ, Hoffman IB, Kueppers F, Fisher D, Idell S: Recombinant alpha 1-antitrypsin Pittsburgh attenuates experimental gram-negative septicemia. Am J Pathol 130:418–426, 1988

    Google Scholar 

  30. Stadnicki A, Niewiarowski T, DeLa Cadena RA, Colman RW: Activation of the contact system and circulating neutrophil elastase in ulcerative colitis patients. 10th World Congress of Gastroenterology, p1166, 1994 (abstract)

  31. Geratz JD, Tidwell RR, Schwab JH, Anderle SK, Pryzwansky KB: Sequential events in the pathogenesis of streptococcal cell wall-induced arthritis and their modulation by bis(5-amidino-2-benzimidazolyl)methane (BABIM). Am J Pathol 136:909–921, 1990

    Google Scholar 

  32. Pixley RA, DeLa Cadena RA, Page JD, Kaufman N, Wyshock EG, Chang A, Taylor FB Jr, Colman RW: The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia:In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons. J Clin Invest 91:61–68, 1993

    Google Scholar 

  33. Silverberg M, Nicoll J, Kaplan A: The mechanism by which the light chain of cleaved HMW-kininogen augments the activation of prekallikrein, factor XI and Hageman factor. Thromb Res 20:173–189, 1980

    Google Scholar 

  34. Woolverton C, White J Jr, Sartor R: Eicosanoid regulation of acute intestinal vascular permeability induced by intravenous peptidoglycan-polysaccharide polymers. Agents Actions 26:301–309, 1989

    Google Scholar 

  35. Adeyemi E, Hodgson H: Faecal elastase reflects disease activity in active ulcerative colitis. Scand J Gastroenterol 27:139–142, 1992

    Google Scholar 

  36. Zeitlin I, Smith A: Mobilization of tissue kallikrein in inflammatory disease of the colon. Gut 14:133–138, 1973

    Google Scholar 

  37. Silverstein E, Fierst S, Simon M, Weinstock J, Friedland J: Angiotensin-converting enzyme in Crohn's disease and ulcerative colitis. Am J Clin Pathol 75:175–178, 1981

    Google Scholar 

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Author notes

  1. Antoni Stadnicki MD

    Present address: VIIth Department of Internal Medicine, Szpital Gorniczy, Silesian Medical School, 41-200 Sosnowiec, Katowice, Poland

Authors and Affiliations

  1. From the Sol Sherry Thrombosis Research Center and Departments of Medicine, Physiology, and Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania

    Antoni Stadnicki MD, Raul A. DeLa Cadena MD, R. Balfour Sartor MD, Diane Bender BS, Charles A. Kettner PhD, Heiko C. Rath MD, Albert Adam PhD &  Robert W. Colman MD

  2. Departments of Medicine, Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

    Antoni Stadnicki MD, Raul A. DeLa Cadena MD, R. Balfour Sartor MD, Diane Bender BS, Charles A. Kettner PhD, Heiko C. Rath MD, Albert Adam PhD &  Robert W. Colman MD

  3. DuPont Merck Pharmaceutical Company, Wilmington, Delaware

    Antoni Stadnicki MD, Raul A. DeLa Cadena MD, R. Balfour Sartor MD, Diane Bender BS, Charles A. Kettner PhD, Heiko C. Rath MD, Albert Adam PhD &  Robert W. Colman MD

  4. Department of Pharmacy, University of Montreal, Montreal, Quebec, Canada

    Antoni Stadnicki MD, Raul A. DeLa Cadena MD, R. Balfour Sartor MD, Diane Bender BS, Charles A. Kettner PhD, Heiko C. Rath MD, Albert Adam PhD &  Robert W. Colman MD

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  1. Antoni Stadnicki MD
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Stadnicki, A., DeLa Cadena, R.A., Sartor, R.B. et al. Selective plasma kallikrein inhibitor attenuates acute intestinal inflammation in lewis rat. Digest Dis Sci 41, 912–920 (1996). https://doi.org/10.1007/BF02091530

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  • DOI: https://doi.org/10.1007/BF02091530

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