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Eicosanoid regulation of acute intestinal vascular permeability induced by intravenous peptidoglycan-polysaccharide polymers

  • Inflammation and Immunomodulation
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Abstract

A model of rapidly developing, self-limited acute vascular permeability changes localized to the gutassociated lymphoid tissue (GALT) of the rat was used to study the role of prostaglandins (PGs), thromboxanes (Txs), and leukotrienes (LTs) in thein vivo regulation of early intestinal inflammatory events. Sprague Dawley rats were pretreated with metabolites, enzyme inhibiors, or receptor antagonists of the arachidonic acid pathway before intravenous injection of sonicated peptidoglycan-polysaccharide polymers derived from group A streptococci (PG-APS, 5 μg rhamnose/g body weight). Rats were killed five minutes after PG-APS injection and were evaluated grossly for petechiae of the intestinal parencyma and lymphoid aggregates.

Indomethacin or dexamethasone increased intestinal injury by PG-APS by inducing mid-small bowel and cecal parenchymal hemorrhage. Indomethacin significantly diminished colonic lymphoid aggregate hemorrhage. PGE1, PGE2, and prostacyclin dramatically inhibited GALT hemorrhage; prostacyclin was the most potent with an effective dose of 0.1 μg/kg. Dazmegrel, a specific Tx synthetase antagonist, significantly inhibited PG-APS-induced vascular permeability. Dazmegrel continued to diminish colonic lympoid aggregated hemorrhage during concurrent treatment with indomethacin, which removed potential endogenous prostaglandin protection. Diethylcarbamazine, a lipoxygenase inhibitor, and FPL-55712, a LT receptor antagonist, inhibited the PG-APS-induced lesions, with FPL-55712 being more potent. LT blockade had a predominant effect on the intestinal parenchymal hemorrhage. We postulate that the normal suppression of inflammation induced by phlogistic bacterialcell wall polymers is PG mediated, and that pathological responses are Tx and LT dependent.

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Abbreviations

PG-APS:

Peptidoglycan-polysaccharide

LTs:

Leukotrienes

PGs:

Prostaglandins

Txs:

Thromboxanes

GALT:

Gut-associated lymphoid tissue

NSAIDs:

Nonsteroidal antiinflammatory drugs

TNF:

Tumor necrosis factor

PMNs:

Polymorphonuclear neutrophils

IL-1:

Interleukin-1

RBC:

Red blood cell

DEC:

Diethylcarbamazine

References

  1. R. B. Sartor, S. K. Anderle, W. J. Cromartie and J. H. Schwab,Localized gut-associated lymphoid tissue hemorrhage induced by intravenous peptidoglycan-polysaccaride polymers. Infect. Immun.51, 521–528 (1986).

    PubMed  Google Scholar 

  2. R. B. Sartor, S. A. Stimpson and S. K. Anderle et al.,Bacterial cell wall-induced GALT hemorrhage: Effect of indigenous intestinal bacterial cell walls and quantitation of tissue specificity. (Abstract). Gastroenterology86, 1232 (1986).

    Google Scholar 

  3. P H. Seidle and K. H. Schleifer,Structure and immunochemistry of peptidoglycan. In (Eds. P. H. Seidle, K. H. Schleifer)Biological Properties of Peptidoglycan. pp. 1–20, Walter de-Gruyter, Berlin 1986.

    Google Scholar 

  4. R. E. Esser, J. H. Schwab, and R. A. Eisenberg,Immunology of peptidoglycan-polysaccharide polymers from bacterial cell walls. InImmunology of the Bacterial Cell Envelope. (Eds. D. E. S. Stewart-Tull, M. Davis), pp. 91–118, John Wiley and Sons, New York 1985.

    Google Scholar 

  5. C. Chetty and J. H. Schwab,Endotoxin-like products of gram-positive bacteria. InChemistry of Endotoxin, (Ed. E. T. Rietschel) Handbook of Endotoxin, vol. 1. pp. 376–410 (1984).

  6. S. A. Stimpson, J. H. Schwab, and J. M. Janusz et al.,Acute and chronic inflammation induced by peptidoglycan structures and polysaccharide complexes. InBiological Properties of Peptidoglycan. (Eds. P. H. Seidl, K. H. Schleifer), pp. 273–290, Walter de Gruyter, Berlin 1986.

    Google Scholar 

  7. H. Hunter, S. K. Anderle and R. R. Brown et al.,Cellmediated immune response during experimental arthritis induced in rats with streptococcal cell walls. Clin. Exp. Immunol.42, 442–449 (1980).

    Google Scholar 

  8. S. Yoshino, W. J. Cromartie and J. H. Schwab,Inflammation induced by bacterial cell wall fragments in the rat air pouch: Comparison of rat strains and measurement of arachidonic acid metabolites. Am. J. Pathol.121, 327–336 (1985).

    PubMed  Google Scholar 

  9. L. A. Bristol, and J. H. Schwab,Relation of IL-1 Production to rat susceptibility in bacterial cell wall arthritis, Fed. Proc. Abstracts, 1986.

  10. R. A. Eisenberg and J. H. Schwab,Arthropathic group A streptococcal cell walls require specific antibody for activation of human complement by both the classical and alternative pathways. Infec. Immun.53, 324–330 (1986).

    Google Scholar 

  11. P. Davies, R. C. Page, and A. C. Allison,Changes in cellular enzyme levels and extracellular release of lysosomal acid hydrolase in macrophages exposed to group A streptococcal wall substance. J. Exp. Med.139, 1262–1282 (1974).

    Article  PubMed  Google Scholar 

  12. P. A. Leong, J. H. Schwab and M. S. Cohen,Interaction of group a streptococcal peptidoglycan-polysaccharide with human polymorphonuclear leukocytes: Implications for Pathogenesis of chronic inflammation. Infect. Immun.45, 160–165 (1985).

    Google Scholar 

  13. D. Powell,Ion and water transport in the intestine. InPhysiology of Membrane Disorders. (Eds. Andreoli et al.), pp. 559–592 Plenum, New York 1986.

    Google Scholar 

  14. S. Stimpson, R. Brown and S. Anderle et al.,Arthropathic properties of cell wall polymers from normal flora bacteria. Infect. Immun.51, 240–249 (1986).

    PubMed  Google Scholar 

  15. A. Fox, R. R. Brown and S. Anderle et al.,Arthropathic properties related to the molecular weight of peptidoglycanpolysaccharide polymers of streptococcal cell walls. Infect. Immun.35, 1003–1010 (1982).

    PubMed  Google Scholar 

  16. R. L. Lorenz, S. Fischer, W. Wober, H. A. Wagner and P. C. Weber,Effects on prostanoid formation and pharmacokinetics of dazmegrel, a novel thromboxane synthesis inhibitor in man. Biochem. Pharmacol.35, 761–766 (1986).

    Article  PubMed  Google Scholar 

  17. M. Parry, M. Randall, E. Hawkeswood, P. Cross and R. Dickinson,Enhanced production of prostacyclin in blood after treatment with selective thromboxane synthetase inhibitor UK-38, 485. Brit. J. Pharmacol.77, 547 A, (1982).

    Google Scholar 

  18. R. Sartor, W. Cromartie, D. Powell and J. Schwab,Granulomatous enterocolitis induced in rats by purified bacterial cell wall fragments. Gastroenterology89, 587–595 (1985).

    PubMed  Google Scholar 

  19. D. Fitzgerald, A. Chance and R. Highsmith et al.,Interleukin-1 as a modulator of endothelial cell shape and function during the inflammatory response. Arth Rheum30, 582A (1987).

    Google Scholar 

  20. J. Bomalaski, M.-J. Chen and M. Clark,Induction of phospholipase A 2 (PLA 2)activity and synthesis of a PLA 2 activating protein by tumor necrosis factor. Arth Rhum30, S28 (1987).

    Google Scholar 

  21. W. Hsueh, F. Gonzalez-Crussi and J. Arroyare,Release of leukotriene C 4 by isolated, perfused rat small intestine in response to platelet-activating factor. J Clin Invest78, 108–114 (1986).

    PubMed  Google Scholar 

  22. W. Stenson, K. Chang and J. Williamson,Tissue differences in vascular permeability induced by leukotriene B 4 and prostaglandin E 2 in the rat. Prostaglandins,32, 5–17 (1986).

    Article  PubMed  Google Scholar 

  23. D. Xiao and L. Levine,Stimulation of arachidonic acid metabolism: Differences in potencies of recombinant human interleukin-1α and interleukin-1β on two cell types. Prostaglandins32, 709–719 (1986).

    Article  PubMed  Google Scholar 

  24. P. Conti, M. Cifone, E. Alesse, M. Reale, C. Fieschi and C. Dinarello,In vitro enhanced thromboxane B 2 release by polymorphonuclear leukocytes and macrophages after treatment with human recombinant interleukin 1. Prostaglandins32, 111–115 (1986).

    Article  PubMed  Google Scholar 

  25. K. Tracey, B. Beutler and S. Lowry et al.,Shock and tissue injury induced by recombinant human cachectin. Science234, 470–474 (1986).

    PubMed  Google Scholar 

  26. W. Hsueh, F. Gonzalez-Crussi and J. ArroyavePlateletactivating factor-induced ischemic bowel necrosis: An investigation of secondary mediators in its pathogenesis. Am. J. Pathol.122, 231–237 (1986).

    PubMed  Google Scholar 

  27. S. Kirkham, K. J. Block, M. B. Bloch, R. P. Perry and W. A. Walker,Immune complex induced enteropathy in the rat. I. Clinical and histological features. Dig. Dis. Science31, 737–743 (1986).

    Article  Google Scholar 

  28. E. Goetzl, D. Payan and D. Goldman,Immunopathogenetic roles of leukotrienes in humans. J. Clin. Immunol.4, 79–84 (1984).

    Article  PubMed  Google Scholar 

  29. L. Brass, C. Shaller and E. Belmonte,Inositol 1, 4, 5-triphosphate-induced granule secretion in platelets. J. Clin. Invest.79, 1269–1275 (1987).

    PubMed  Google Scholar 

  30. W. Fang, A. Broughton and E. Jacobson,Indomethaciniduced intestinal inflammation. Am. J. Dig. Dis.22, 749–760 (1977).

    Article  PubMed  Google Scholar 

  31. I. Bjarnason, G. Zanelli, T. Smith, P. Prouse, P. Williams, P. Smethurst, G. Delacey, M. Gumpel and A. Levi,Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans. Gastroenterology93, 480–489 (1987).

    PubMed  Google Scholar 

  32. D. Engineer, U. Niederhauser, P. Piper and P. Sirois,Release of mediators of anaphylaxis: inhibition by prostaglandin synthesis and the modification of release of slow reacting substance of anaphylaxis and histamine. Br. J. Pharmacol.62, 61–66 (1978).

    PubMed  Google Scholar 

  33. R. B. Sartor, T. M. Bond and J. H. Schwab,Systemic uptake and intestinal effects of luminal bacterial cell wall polymers in rats with acute colonic injury. Infect. Immun., in press (1988).

  34. J. S. Redfern, A. J. Blair, E. Lee and M. Feldman,Gastro-intestinal ulcer formation in rabbits immunized with prosta-glandin E 2, Gastroenterology93, 44–52 (1987).

    Google Scholar 

  35. T. H. Kent, R. M. Cardelli and F. W. Stamler,Small intestinal ulcers and intestinal flora in rats given indomethacin. Am. J. Pathol.34, 237–245 (1969).

    Google Scholar 

  36. A. Robert and T. Asano,Resistance of germ free rats to indomethacin-induced intestinal lesions. Prostaglandins14, 333–341 (1977).

    Article  PubMed  Google Scholar 

  37. H. J. Kaufmann and H. L. Taubin,Nonsteroidal anti-inflammatory drugs activate quiescent inflammatory bowel disease. Ann. Int. Med.107, 513–516 (1987).

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Core Center in Diarrheal Diseases, University of North Carolina at Chapel Hill, 27599, Chapel Hill, NC, USA

    C. J. Woolverton & R. B. Sartor

  2. Department of Medicine, University of North Carolina at Chapel Hill, 27599, Chapel Hill, NC, USA

    J. J. White Jr. & R. B. Sartor

Authors
  1. C. J. Woolverton
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  2. J. J. White Jr.
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  3. R. B. Sartor
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Additional information

Supported by funds of the National Institutes of Health, Grants K01 AM-01112, DK-34987, and AR-25733, and the National Foundation for Ileitis and Colitis.

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Woolverton, C.J., White, J.J. & Sartor, R.B. Eicosanoid regulation of acute intestinal vascular permeability induced by intravenous peptidoglycan-polysaccharide polymers. Agents and Actions 26, 301–309 (1989). https://doi.org/10.1007/BF01967294

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  • DOI: https://doi.org/10.1007/BF01967294

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