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Chemotactic activity in inflammatory bowel disease

Role of leukotriene B4

Abstract

An important histologic feature of inflammatory bowel disease (IBD) is infiltration of the colonic mucosa with neutrophils. To investigate the nature of the chemotactic agents responsible for this infiltration, colonic mucosa from three normals and nine patients with inflammatory bowel disease (seven ulcerative colitis, two Crohn's colitis) was assayed for chemotactic activity for human neutrophilsin vitro in a Boyden chamber. There was more (>10-fold more) chemotactic activity in homogenates of inflammatory bowel disease mucosa than in homogenates of normal colonic mucosa. Analysis of the chemotactic activity in the inflammatory bowel disease mucosa revealed that most was lipid extractable. Moreover, when the lipid extract was fractionated by reverse-phase high-pressure liquid chromatography, the only fraction with significant chemotactic activity was the fraction that coeluted with leukotriene B4. The chemotactic response to IBD mucosa was blocked by anti-LTB4 antisera. The amount of chemotactic activity in lipid extracts of different inflammatory bowel disease specimens correlated well with the concentration of leukotriene B4 measured by UV absorbance (250 ng/g of mucosa). These data suggest that leukotriene B4 is an important stimulus to neutrophil chemotaxis in inflammatory bowel disease and, thus, may play a major role in the amplification of the inflammatory response in this condition.

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References

  1. 1.

    Lauritsen K, Hansen J, Bytzer P, Bukhave K, Rask-Madsen J: Effects of sulfasalazine and disodium azodisalicylate on colonic PGE2 concentrations determined by equilibriumin vivo dialysis of faeces in patients with ulcerative colitis and healthy controls. Gut 25:1271–1278, 1984

    Google Scholar 

  2. 2.

    Boughton-Smith NK, Hawkey CJ, Whittle BJR: Biosynthesis of lipoxygenase and cyclooxygenase products from [14C]arachidonic acid by human colonic mucosa. Gut 24:1176–1182, 1983

    Google Scholar 

  3. 3.

    Rampton DS, Hawkey CF: Prostaglandins and ulcerative colitis. Gut 25:1399–1413, 1985

    Google Scholar 

  4. 4.

    Sharon P, Stenson WF: Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroenterology 86:453–460, 1984

    Google Scholar 

  5. 5.

    Ford-Hutchinson AW, Bray MA, Doig MV, Shipley ME, Smith JH: Leukotriene B, a potent chemotactic and aggregating substance released from polymorphonuclear leukocytes. Nature 266:264–265, 1984

    Google Scholar 

  6. 6.

    Dahlen SE, Bjork J, Hedqvist P, Arfors KE, Hammarstrom S, Lindgren JA, Samuelsson B: Leukotrienes promote plasma leakage and leukocyte adhesion in post-capillary venules:In vivo effects with relevance to the acute inflammatory response. Proc. Natl Acad Sci USA 78:2887–2891, 1981

    Google Scholar 

  7. 7.

    Saverymuttu SH, Peters AM, Lavender JP, Chadwick VS, Hodgson HJ:In vivo assessment of granulocyte migration in diseased bowel in Crohn's disease. Gut 26:378–383, 1985

    Google Scholar 

  8. 8.

    Saverymuttu SH: Chadwick VS, Hodgson HJ: Granulocyte migration in ulcerative colitis. Eur J Clin Invest 15:60–68, 1985

    Google Scholar 

  9. 9.

    Gallin JI Clark RA, Kaplan AP: Granulocyte chemotaxis, an improvedin vitro assay employing51Cr-labeled granulocytes. J Immunol 110:233–240, 1973

    Google Scholar 

  10. 10.

    Boyum A: Isolation of mononuclear cells and granulocytes from human blood. Isolation of mononuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1g. Scand J Lab Clin Invest 21(Suppl 97):77, 1968

    Google Scholar 

  11. 11.

    Borgeat P, Samuelsson B: Transformation of arachidonic acid by rabbit polymorphonuclear leukocytes. J Biol Chem 254:2643–2646, 1979

    Google Scholar 

  12. 12.

    Krawisz JE, Sharon P, Stenson WF: Quantitative assay for acute intestinal inflammation based on myeloperoxidase assay. Gastroenterology 87:1344–1350, 1984

    Google Scholar 

  13. 13.

    Wilkinson PC: Chemotaxis and Inflammation, 2nd ed. Edinburgh, Churchill Livingston, 1982, p 93

    Google Scholar 

  14. 14.

    Flower RJ, Blackwell GJ: The importance of phospholipase A2 in prostaglandin biosynthesis. Biochem Pharmacol 25:285–291, 1976

    Google Scholar 

  15. 15.

    Kuo CG, Lewis MT, Jakschik B: Leukotriene D4 and E4 formation by plasma membrane bound enzymes. Prostaglandins 28:929–937, 1984

    Google Scholar 

  16. 16.

    Bach MK: Mediators of anaphylaxis and inflammation. Annu Rev Microbiol 36:371–413, 1982

    Google Scholar 

  17. 17.

    Parker CW: Mediators: Release and function.In Fundamental Immunology. WE Paul (ed). New York: Raven Press, 1984, pp 697–750

    Google Scholar 

  18. 18.

    Sharon P, Ligumsky M, Rachmilewitz D, Zor U: Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine. Gastroenterology 75:638–640, 1978

    Google Scholar 

  19. 19.

    Gould SR: Assay of prostaglandin-like substances in faeces and their measurement in ulcerative colitis. Prostaglandins 11:489–497, 1981

    Google Scholar 

  20. 20.

    Gould SR, Brash AR, Conolly ME, Lennard-Jones JE: Studies of prostaglandins and sulphasalazine in ulcerative colitis. Prostaglandins, Leukotrienes, and Medicine 6:165–182, 1981

    Google Scholar 

  21. 21.

    Lauritsen K, Laursen LS, Bukhave K, Rask-Madsen J: Effects of systemic prednisolone on arachidonic acid metabolites determined by equilibriumin vivo dialysis of rectum in severe relapsing ulcerative colitis. Gastroenterology 88:1466, 1985 (abstract)

    Google Scholar 

  22. 22.

    Schiffman E, Corcoran BA, Wahl SA:N-Formylmethionyl peptides as chemoattractants for leukocytes. Proc Natl Acad Sci USA 72:1059–1062, 1975

    Google Scholar 

  23. 23.

    Franklin ML, Cisneros R, Onderdonk AB: Chemotactic factors in the stool of patients with ulcerative colitis. Am J Clin Nutr 33:2540, 1980 (abstract)

    Google Scholar 

  24. 24.

    Peskar BM, Dreyling KW, Hoppe U, Schaarschmidt K, Goebell H, Peskar BA: Formation of sulfidopeptide-leukotrienes (SP-LT) in normal human colonic tissue, colonic carcinoma, and Crohn's disease. Gastroenterology 88:1537, 1985 (abstract)

    Google Scholar 

  25. 25.

    Sharon P, Stenson WF: Metabolism or arachidonic acid in acetic acid colitis in rats: Similarity to human inflammatory bowel disease. Gastroenterology, 88:55–63, 1985

    Google Scholar 

  26. 26.

    Klickstein LB, Shapleigh C, Goetzl EJ: Lipoxygenation of arachidonic acid as a source of polymorphonuclear leukocyte chemotactic factors in synovial fluid and tissues in rheumatoid arthritis and spondyloarthritis. J Clin Invest 66:1166–1120, 1980

    Google Scholar 

  27. 27.

    Rae SA, Davidson EM, Smith MJH: Leukotriene B4, an inflammatory mediator in gout. Lancet 2:1122–1123, 1982

    Google Scholar 

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Correspondence to William F. Stenson MD.

Additional information

This work is supported by a grant from the National Foundation for Ileitis and Colitis and grant AM-33165 from the National Institutes of Health.

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Lobos, E.A., Sharon, P. & Stenson, W.F. Chemotactic activity in inflammatory bowel disease. Digest Dis Sci 32, 1380–1388 (1987). https://doi.org/10.1007/BF01296664

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Key Words

  • inflammatory bowel disease
  • Crohn's disease
  • ulcerative colitis
  • chemotaxis
  • neutrophil