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Effects of neutrophil-derived oxidants on intestinal permeability, electrolyte transport, and epithelial cell
M B Grisham1, T S Gaginella, C von Ritter
1Department of Physiology and Biophysics, LSU Medical Center 71130.
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-to-lumen 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 HOCl, 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 HOCl 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 Tau NHCl 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.
Insights
Polymorphonuclear leukocyte (PMN)-derived oxidants like hydrogen peroxide and hypochlorous acid increase intestinal permeability and damage epithelial cells. These findings suggest a role for PMN oxidants in bowel inflammation.
Area of Science:
- Gastroenterology
- Cell Biology
- Immunology
Background:
- Intestinal inflammation is linked to increased mucosal permeability, fluid loss, and epithelial damage.
- Polymorphonuclear leukocytes (PMNs) release oxidants during inflammation.
Purpose of the Study:
- To investigate the effects of PMN-derived oxidants on ileal mucosal permeability in vivo.
- To assess the impact of these oxidants on electrolyte transport and epithelial cell viability in vitro.
Main Methods:
- In vivo: Measured blood-to-lumen clearance of [51Cr]EDTA to assess mucosal permeability.
- In vitro: Examined electrolyte transport (short-circuit current) and epithelial cell viability in rat ileum and cultured cells.
Main Results:
- Hydrogen peroxide (H2O2), hypochlorous acid (HOCl), and monochloramine (NH2Cl) increased mucosal permeability in a dose-dependent manner.
- NH2Cl and H2O2 increased short-circuit current in rat ileum, but HOCl and Taurine monochloramine (TauNHCl) did not.
- NH2Cl and HOCl caused dose-dependent injury to cultured intestinal epithelial cells, while H2O2 and TauNHCl were non-toxic.
Conclusions:
- PMN-derived oxidants, particularly HOCl and NH2Cl, can enhance intestinal mucosal permeability.
- These oxidants may contribute to electrolyte transport alterations and epithelial cell injury observed in acute bowel inflammation.