| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 5 1007-G1021, Copyright © 1997 by American Physiological Society
ARTICLES |
M. J. Menconi, A. L. Salzman, N. Unno, R. M. Ezzell, D. M. Casey, D. A. Brown, Y. Tsuji and M. P. Fink
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
We previously demonstrated that ileal mucosal acidosis in pigs reversibly increases intestinal permeability to hydrophilic macromolecules, even in the absence of tissue hypoxia [A.L. Salzman, H. Wang, P.S. Wollert, T.J. Vandermeer, C.C. Compton, A.G. Denenberg, and M.P. Fink. Am. J. Physiol. 266 (Gastrointest, Liver Physiol, 29): G633-G646, 1994]. In an effort to further explore the mechanism(s) underlying this phenomenon, we examined the effect of acidic pH on the permeability characteristics of cultured Caco-2BBe (human intestinal epithelial) cells grown as monolayers on permeable supports. Permeability was determined by measuring the mucosal-to-basolateral flux of fluorescein disulfonic acid (FS; mol wt 478 Dal, fluorescein isothiocyanate-labeled dextran (FD4; average mol wt 4 kDa), or [3H]mannitol. Incubation of monolayers under hypercarbic conditions or with acidific bicarbonate-free medium significantly increased permeability to FS, FD4, and mannitol in a manner dependent on both time and pH. Incubation in medium at pH 5.43 for 24 h increased the release of lactate dehydrogenase and decreased the intensity of staining with calcein-acetoxymethyl ester, findings that are indicative of plasma membrane injury; nevertheless, the percentage of nonviable cells did not increase. Ultrastructural analyses revealed evidence of increased paracellular trafficking of horseradish peroxidase after incubation of monolayers under acidic conditions. Fluorescence confocal microscopy and temperature studies demonstrated that incubation at pH 5.43 induced an increase in both the intracellular uptake of FD4 and the activation energy for FS permeation across Caco-2BBe monolayers, respectively, suggesting increased transcellular permeation. Exposure to acidic conditions also decreased cellular levels of ATP. We conclude that acidosis increases both paracellular and transcellular permeability to hydrophilic macromolecules and leads to depletion of ATP.
This article has been cited by other articles:
|
|
 |
|
  K. G. Raman, P. L. Sappington, R. Yang, R. M. Levy, J. M. Prince, S. Liu, S. K. Watkins, A. M. Schmidt, T. R. Billiar, and M. P. Fink The role of RAGE in the pathogenesis of intestinal barrier dysfunction after hemorrhagic shock Am J Physiol Gastrointest Liver Physiol, October 1, 2006; 291(4): G556 - G565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Liu, D. B. Stolz, P. L. Sappington, C. A. Macias, M. E. Killeen, J. J. Tenhunen, R. L. Delude, and M. P. Fink HMGB1 is secreted by immunostimulated enterocytes and contributes to cytomix-induced hyperpermeability of Caco-2 monolayers Am J Physiol Cell Physiol, April 1, 2006; 290(4): C990 - C999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Sappington, X. Han, R. Yang, R. L. Delude, and M. P. Fink Ethyl Pyruvate Ameliorates Intestinal Epithelial Barrier Dysfunction in Endotoxemic Mice and Immunostimulated Caco-2 Enterocytic Monolayers J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 464 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Banan, J. Z. Fields, A. Farhadi, D. A. Talmage, L. Zhang, and A. Keshavarzian The beta 1 Isoform of Protein Kinase C Mediates the Protective Effects of Epidermal Growth Factor on the Dynamic Assembly of F-Actin Cytoskeleton and Normalization of Calcium Homeostasis in Human Colonic Cells J. Pharmacol. Exp. Ther., June 1, 2002; 301(3): 852 - 866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Banan, J. Z. Fields, D. A. Talmage, Y. Zhang, and A. Keshavarzian PKC-{beta}1 mediates EGF protection of microtubules and barrier of intestinal monolayers against oxidants Am J Physiol Gastrointest Liver Physiol, September 1, 2001; 281(3): G833 - G847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. G. Dickman, S. J. Hempson, J. Anderson, S. Lippe, L. Zhao, R. Burakoff, and R. D. Shaw Rotavirus alters paracellular permeability and energy metabolism in Caco-2 cells Am J Physiol Gastrointest Liver Physiol, October 1, 2000; 279(4): G757 - G766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. B Jijon, T. Churchill, D. Malfair, A. Wessler, L. D Jewell, H. G Parsons, and K. L Madsen Inhibition of poly(ADP-ribose) polymerase attenuates inflammation in a model of chronic colitis Am J Physiol Gastrointest Liver Physiol, September 1, 2000; 279(3): G641 - G651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Peiffer, A.-B. Blanc-Potard, M.-F. Bernet-Camard, J. Guignot, A. Barbat, and A. L. Servin Afa/Dr Diffusely Adhering Escherichia coli C1845 Infection Promotes Selective Injuries in the Junctional Domain of Polarized Human Intestinal Caco-2/TC7 Cells Infect. Immun., June 1, 2000; 68(6): 3431 - 3442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Dickinson, R. Tuncer, E. Nadler, P. Boyle, S. Alber, S. Watkins, and H. Ford NOX, a novel nitric oxide scavenger, reduces bacterial translocation in rats after endotoxin challenge Am J Physiol Gastrointest Liver Physiol, December 1, 1999; 277(6): G1281 - G1287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Lambert, C. V. Gisolfi, D. J. Berg, P. L. Moseley, L. W. Oberley, and K. C. Kregel Molecular Biology of Thermoregulation: Selected Contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress J Appl Physiol, April 1, 2002; 92(4): 1750 - 1761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. U. Khan, R. L. Delude, Y. Y. Han, P. L. Sappington, X. Han, J. A. Carcillo, and M. P. Fink Liposomal NAD+ prevents diminished O2 consumption by immunostimulated Caco-2 cells Am J Physiol Lung Cell Mol Physiol, May 1, 2002; 282(5): L1082 - L1091. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
