Skip to main content

Advertisement

SpringerLink
Log in

Role of neutrophils and mast cells in acute indomethacin-induced small bowel injury in the rat

  • Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

The aim of this study was to determine whether the injury to the rat jejunum during the first 4.5h exposure to indomethacin is due to an influx of neutrophils or degranulation of resident mast cells. Indomethacin and vehicle both caused changes in villous morphology (length, width, etc.) while only indomethacin injured the small bowel, as indicated by increased histological lesion score and51Cr-ethylene diamine tetraacetate (EDTA) flux across the intestinal epithelium. Immunohistochemical staining showed the same small increase in neutrophil density (predominantly in the submucosa) following exposure to vehicle as following exposure to indomethacin. Chronic oral administration of indomethacin for 48 h did cause increased tissue neutrophil density compared to that in vehicle-fed controls. Mast cell depletion (using dexamethasone) did not alter either the indomethacin-induced increase in51Cr-EDTA clearance or the increase in neutrophil density caused by the vehicle and by indomethacin. However, the lesion score following exposure to indomethacin was significantly lower in mast-cell-depleted animals than in control animals. We conclude that the acute phase of indomethacin-induced intestinal injury is not associated with neutrophil influx. Increased neutrophils seen after chronic indomethacin may result from injury rather than be causative. Mast cells appear to exacerbate the initial stages of indomethacin-induced intestinal injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wallace JL, Keenan CM, Granger DN. Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophil-dependent process. Am J Physiol 1990;259:G462–467.

    PubMed  CAS  Google Scholar 

  2. Alican I, Coskun T, Corak A, et al. Role of neutrophils in indomethacin-induced gastric mucosal lesions in rats. Inflamm Res 1995;44:164–168.

    Article  PubMed  CAS  Google Scholar 

  3. Lee M, Aldred K, Lee E, Feldman M. Aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process in rats. Am J Physiol 1992;263:G920–926.

    PubMed  CAS  Google Scholar 

  4. Trevethick MA, Clayton NM, Bahl AK, et al. Neutrophil depletion does not prevent indomethacin-induced ulceration of the rat gastric antrum. Agents Actions 1994;41:C226–227.

    Article  Google Scholar 

  5. Wallace JL, Arfors KE, McKnight GW. A monoclonal antibody against the CD 18 leukocyte adhesion molecule prevents indomethacin-induced gastric damage in the rabbit. Gastroenterology 1991;100:878–883.

    PubMed  CAS  Google Scholar 

  6. Wallace JL, McKnight W, Miyasaka M, et al. Role of endothelial adhesion molecules in NSAID-induced gastric mucosal injury. Am J Physiol 1993;265:G993–998.

    PubMed  CAS  Google Scholar 

  7. Chmaisse HM, Antoon JS, Kvietys PR, et al. Role of leukocytes in indomethacin-induced small bowel injury in the rat. Am J Physiol 1994;266:G239–246.

    PubMed  CAS  Google Scholar 

  8. Yamada T, Deitch E, Specian RD, et al. Mechanisms of acute and chronic intestinal inflammation induced by indomethacin. Inflammation. 1993;17:641–662.

    Article  PubMed  CAS  Google Scholar 

  9. Melarange R, Gentry C, Toseland CDN, et al. Neutropenia does not prevent etodolac or indomethacin-induced gastrointestinal damage in the rat. Dig Dis Sci 1995;40:2694–2703.

    Article  PubMed  CAS  Google Scholar 

  10. Miura S, Suematsu M, Tanaka S, et al. Microcirculatory disturbance in indomethacin-induced intestinal ulcer. Am J Physiol 1991;261:G213–219.

    PubMed  CAS  Google Scholar 

  11. Asako H, Kubes P, Wallace J, et al. Indomethacin-induced leukocyte adhesion in mesenteric venules—role of lipoxygenase products. Am J Physiol 1992;262:G903–908.

    PubMed  CAS  Google Scholar 

  12. Kurose I, Wolf R, Miyasaka M, et al. Microvascular dysfunction induced by non-steroidal anti-inflammatory drugs: Role of leukocytes. Am J Physiol 1996;270:G363–369.

    PubMed  CAS  Google Scholar 

  13. Selye H, Jean P, Contin M. Prevention by stress and cortisol of gastric ulcers normally produced by 48/80. Proc Soc Exp Biol Med 1960;103:444–446.

    PubMed  CAS  Google Scholar 

  14. Karmeli F, Eliakim R, Okon E, et al. Gastric mucosal damage by ethanol is mediated by substance P and prevented by ketotifen, a mast cell stabilizer. Gastroenterology 1991;100:1206–1216.

    PubMed  CAS  Google Scholar 

  15. Hogaboam CM, Bissonnette EY, Chin BC, et al. Prostaglandins inhibit inflammatory mediator release from rat mast cells. Gastroenterology 1993;104:122–129.

    PubMed  CAS  Google Scholar 

  16. Crissinger KD, Kvietys PR, Granger DN. Pathophysiology of gastrointestinal mucosal permeability. J Int Med 1990;228(Suppl 1):145–154.

    Google Scholar 

  17. Rentrop M, Knapp B, Winter H, et al. Aminoalkylsilane-treated glass sides as support of in situ hybridization of keratin cDNAs to frozen tissue sections under varying fixation and pretreatment conditions. Histochem J 1986;18:271–276.

    Article  PubMed  CAS  Google Scholar 

  18. Leung FW, Miller JC, Reedy TJ, et al. Exogenous prostaglandin protects against acid-induced deep mucosal injury by stimulating alkaline secretion in rat duodenum. Dig Dis Sci 1989;34:1686–1691.

    Article  PubMed  CAS  Google Scholar 

  19. Soda K, Kawabori S, Perdue M, et al. macrophage engulfment of mucosal mast cells in rats treated with dexamethasone. Gastroenterology 1991;100:929–937.

    PubMed  CAS  Google Scholar 

  20. Anthony A, Dhillon AP, Nygård G, et al. Early histological features of small intestinal injury induced by indomethacin. Aliment Pharmacol Ther 1993;7:29–40.

    Article  PubMed  CAS  Google Scholar 

  21. Nygård G, Anthony A, Piasecki C, et al. Acute indomethacin-induced jejunal injury in the rat: Early morphological and biochemical changes. Gastroenterology 1994;106:567–575.

    PubMed  Google Scholar 

  22. Slater C, House SD. Effects of non-steroidal anttinflammatory drugs on microvascular dynamics. Microvasc Res 1993;45:166–179.

    Article  PubMed  CAS  Google Scholar 

  23. Yoshida N, Takemura T, Granger DN, et al. Molecular determinants of aspirin-induced neutrophil adherence to endothelial cells. Gastroenterology 1993;105:715–724.

    PubMed  CAS  Google Scholar 

  24. Andrews F, Malcontenti-Wilson C, O'Brien P, Effect of non-steroidal anti-inflammatory drugs on LFA-1 and ICAM-1 expression in gut mucosa. Am J Physiol 1994;266:G657-G664.

    PubMed  CAS  Google Scholar 

  25. Jackson GDF, Dai Y. Biliary tumour necrosis factor alpha mediates endotoxin-induced gastrointestinal damage. Clin Immunol Immunopathol 1995;76:S41.

    Google Scholar 

  26. Rosam AC, Wallace JL, Whittle BJR. Potent ulcerogenic actions of platelet-activating factor on the stomach. Nature 1986;319:54–56.

    Article  PubMed  CAS  Google Scholar 

  27. D'incà R, Hunt RH, Perdue MH. Mucosal damage during intestinal anaphylaxis in the rat. Effect of betamethasone and disodium cromoglycate. Dig Dis Sc 1992;37:1704–1708.

    Article  Google Scholar 

  28. Galli SJ, Wershil BK, Bose R, et al. Ethanol-induced acute gastric injury in mast cell-deficient and congenic normal mice. Evidence that mast cell can augment the area of damage. Am J Pathol 1988;128:131–140.

    Google Scholar 

  29. Takeuchi K, Nishiwaki H, Okabe S. Cytoprotective action of mast cell stabilizers against ethanol-induced gastric lesions in rats. Jpn J Pharmacol 1986;42:297–307

    Article  PubMed  CAS  Google Scholar 

  30. Beck PL, Morris GP, Wallace JL. Reduction of ethanol-induced gastric damage by sodium cromoglycate and FPL-52694. Role of leukotrienes, prostaglandins and mast cells in the protective mechanism. Can J Physiol Pharmacol 1989;67:287–293.

    PubMed  CAS  Google Scholar 

  31. Colton DG, Reiffenstein JC, Buyniski JP. BMY-26517-31, a mast cell stabilizer with cytoprotective properties (abstract). Gastroenterology 1985;88(5) part 2:1354.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Physiology and Pharmacology, University of New South Wales, 2052, Sydney, Australia

    Juliette S. Antoon & Michael A. Perry

Authors
  1. Juliette S. Antoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael A. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Antoon, J.S., Perry, M.A. Role of neutrophils and mast cells in acute indomethacin-induced small bowel injury in the rat. J Gastroenterol 32, 747–757 (1997). https://doi.org/10.1007/BF02936950

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02936950

Key words

Search

Navigation