Skip to main content
Log in

Effects of neutrophil-derived oxidants on intestinal permeability, electrolyte transport, and epithelial cell viability

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

There are several pathophysiologic conditions in which intestinal inflammation is associated with enhanced mucosal permeability, fluid loss, and epithelial cell injury. The objective of this study was to determine the effects of polymorphonuclear leukocyte (PMN) -derived oxidants on ileal mucosal permeability in vivo as well as electrolyte transport and epithelial cell viability in vitro. Using blood-tolumen clearance of [51Cr]EDTA as a measure of mucosal permeability, we found that luminal perfusion with hydrogen peroxide (H2O2), hypochlorous acid (HOCl), or monochloramine (NH2Cl) produced a dose-dependent increase in mucosal permeability. Perfusion with 0.1 mM, 0.5 mM, and 1.0 mM oxidant produced a 2±1, 5±2, and 11±5-fold increase in mucosal permeability for H2O2, a 2±1, 8±3, and 36±12-fold increase for HOC1, and a 3±1, 11±2, and 30±7-fold increase for NH2Cl. Taurine monochloramine (TauNHCl) was ineffective in enhancing the blood-to-lumen clearance of [51Cr]EDTA. Furthermore, 0.01 mM and 0.1 mM NH2Cl and H2O2 produced significant increases in short-circuit current across rat ileum in vitro, whereas HOC1 and TauNHCl were without effect. Tissue resistance and potential difference were not altered, suggesting that NH2Cl, HOCl, and H2O2 were not cytotoxic under these conditions. Cultured intestinal epithelial cells exposed to NH2Cl and HOCl were injured in a dose-dependent manner in vitro, whereas H2O2 and TauNHCl were nontoxic. Taken together, our data suggest that PMN-derived oxidants may mediate the enhanced mucosal permeability, electrolyte transport, and epithelial cell injury associated with acute inflammation of the bowel.

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

Access this article

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. Earnest, P. L. andJ. S. Trier. 1989. Radiation enteritis and colitis.In Gastrointestinal Disease. M. H. Sleisenger and J. S. Fordtran, editors. W. B. Saunders, Philadelphia. 1369–1382.

    Google Scholar 

  2. Granger, D. N., M. E. Hollwarth, andD. A. Parks. 1986. Ischemia-reperfusion injury: Role of oxygen-derived free radicals.Acta Physiol. Scand. 548(Suppl.):47–63.

    Google Scholar 

  3. Riddell, R. 1988. Pathology of idiopathic inflammatory bowel disease.In Inflammatory Bowel Disease. J. B. Kirsner and R. G. Shorter, editors. Lea and Febinger, Philadelphia. 329–350.

    Google Scholar 

  4. Klebanoff, S. J. 1988. Phagocytic cells: Products of oxygen metabolism.In Inflammation, Basic Principles and Clincal Correllates. J. I. Gallin, I. M. Goldstein, and R. Snyderman editors. Raven Press, New York. 391–444.

    Google Scholar 

  5. Thomas, E. L., M. B. Grisham, andM. M. Jefferson. 1983. Myeloperoxidase dependent effects of amines on functions of isolated neutrophils.J. Clin. Invest. 72:441–454.

    Google Scholar 

  6. Weiss, S. J., R. Klein, A. Slivka, andM. Wei. 1982. Chlorination of taurine by human neutrophils. Evidence for hypochlorous acid generation.J. Clin. Invest. 70:598–607.

    Google Scholar 

  7. Grisham, M. B., M. M. Jefferson, andE. L. Thomas. 1984. Chlorination of endogenous amines by isolated neutrophils.J. Biol. Chem. 259:10404–10413.

    Google Scholar 

  8. Grisham, M. B., M. M. Jefferson, andE. L. Thomas. 1984. Role of monochloramine in the oxidation of erythrocyte hemoglobin by stimulated neutrophils.J. Biol. Chem. 259:6757–6765.

    Google Scholar 

  9. Thomas, E. L., M. B. Grisham, andM. M. Jefferson. 1986. Cytotoxicity of chloramines.Methods Enzymol. 132:585–593.

    Google Scholar 

  10. Thomas, E. L., M. B. Grisham, andM. M. Jefferson. 1986. Preparation and characterization of chloramines.Methods Enzymol. 132:569–584.

    Google Scholar 

  11. Bern, M. J., C. W. Sturbaum, S. S. Karayalcin, H. M. Berschneider, J. T. Wachsman, andD. W. Powell. 1989. Immune system control of rat and rabbit colonie electrolyte transport. Role of prostaglandins and enteric nervous system.J. Clin. Invest. 83:1810–1820.

    Google Scholar 

  12. Tamai, H., M. B. Grisham, andT. S. Gaginella. 1989. Chloramine oxidants induce electrolyte secretion in the rat colon.Gastroenterology 96:A503 (abstract).

    Google Scholar 

  13. Von Ritter, E. Sekizuka, M. B. Grisham, andD. N. Granger. 1988. The chemotactic peptideN-formyl methionyl-leucyl-phenylalanine increases mucosal permeability in the distal ileum of the rat.Gastroenterology 95:651–656.

    Google Scholar 

  14. Von Ritter, C., M. B. Grisham, M. Hollwarth, W. Inauen, andD. N. Granger. 1989. Neutrophil-derived oxidants mediate formyl-methionyl-leucyl-phenylalaine-induced increases in mucosal permeability in rats.Gastroenterology 97:778–780.

    Google Scholar 

  15. Von Ritter, C., M. B. Grisham, andD. N. Granger. 1989. Sulfasalazine metabolites attenuate formyl-methionyl-leucyl-phenylalanine induced mucosal injury in rat ileum.Gastroenterology 96:811–816.

    Google Scholar 

  16. Chance, B., H. Sies, andA. Boveris. 1979. Hydroperoxide metabolism in mammalian organs.Physiol Rev. 59:527–605.

    Google Scholar 

  17. Thomas, E. L. 1979. Myeloperoxidase, hydrogen peroxide, chloride antimicrobial system: Effect of exogenous amines on antibacterial action againstE. Coli. Infect. Immun. 25:110–116.

    Google Scholar 

  18. Cohen, G. 1985. The Fenton reaction.In Handbook of Methods for Oxygen Radical Research. R. A. Greenwald, editor. CRC Press, Boca Raton. 55–64.

    Google Scholar 

  19. Halliwell, B., andJ. M. C. Gutteridge. 1986. Oxygen free radicals and iron in relation to biology and medicine: Some problems and concepts.Arch. Biochem. Biophys. 246:501–514.

    Google Scholar 

  20. Sekizuka, E., M. B. Grisham, M. Li, E. A. Deitch, andD. N. Granger. 1988. Inflammation-induced hyperemia in the rat: role of neutrophils.Gastroenterology 95:1528–1534.

    Google Scholar 

  21. Welsh, M. J., D. N. Shasby, andR. M. Husted. 1985. Oxidants increase paracellular permeability in a cultured epithelial cell line.J. Clin. Invest. 76:1155–1168.

    Google Scholar 

  22. Shasby, D. N., andF. Hampson. 1989. Effects of chlorinated amines on endothelial and epithelial barriers in vitro and ex vivo.Exp. Lung Res. 15:345–357.

    Google Scholar 

  23. Grisham, M. B., C. Von Ritter, B. F. Smith, J. T. Lamont, andD. N. Granger. 1987. Interaction between oxygen radicals and gastric mucin.Am. J. Physiol. 253:G93-G96.

    Google Scholar 

  24. Vissers, M. C. M., W. A. Day, andC. C. Winterbourn. 1985. Neutrophils adherent to a nonphagocytosable surface (glomerular basement membrane) produce oxidants only at the site of attachment.Blood 66:161–166.

    Google Scholar 

  25. Nathan, C. F. 1987. Neutrophil activation on biological surfaces: massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes.J. Clin. Invest. 80:1550–1560.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by grants from the National Institutes of Health (DK 39168 and DK 33594).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grisham, M.B., Gaginella, T.S., von Ritter, C. et al. Effects of neutrophil-derived oxidants on intestinal permeability, electrolyte transport, and epithelial cell viability. Inflammation 14, 531–542 (1990). https://doi.org/10.1007/BF00914274

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00914274

Keywords

Navigation