The effect of hypoxia on permeability and bacterial translocation in Caco-2 adult and I-407 fetal enterocyte cell culture models.
Hypoxia has been implicated in the breakdown of the intestinal epithelial barrier in animals, leading to bacterial translocation (BT); however, the mechanism of this hypoxic insult is unknown. To determine the effects of hypoxic injury in vitro on epithelial membrane integrity, transepithelial electrical resistance (TEER), mannitol permeability (Ma-Pm), and BT were measured in both an adult (Caco-2) and fetal (I-407) intestinal epithelial cell culture model. Caco-2 adult and I-407 fetal epithelial cell monolayers were treated with or without bacteria (1 x 10(7) Escherichia coli. C-25), and then incubated under either normoxic (5% CO(2) in room air) or hypoxic (5% CO(2) and 95% N(2)) conditions at 37 degrees C for 6 h. Hypoxia caused a 10% increase in Ma-Pm in the I-407 fetal cell model independent of the bacterial challenge. In contrast, a bacterial challenge in the Caco-2 adult model caused a 485% increase in Ma-Pm independent of hypoxia. Neither hypoxia, nor C-25 bacteria, for 6 h caused BT in either cell culture model. In the adult cell culture model, bacteria appear to mediate changes in epithelial barrier function, with hypoxia having no effect. On the other hand, hypoxia is the major factor in the loss of epithelial barrier function in fetal epithelium, but has no effect on adult epithelium. The data suggest that the breakdown of barrier function caused by a hypoxic insult is the primary stimulus for subsequent BT in neonates.
Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan Medical School, Mott F3970, Box 0245, Ann Arbor, MI 48109, USA.
Y
Y
Tazuke
R A
RA
Drongowski
D H
DH
Teitelbaum
A G
AG
Coran
D018988:Bacterial Translocation / Q000502:physiology*; D018938:Caco-2 Cells; D015687:Cell Hypoxia / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D017097:Electric Impedance; D020895:Enterocytes; D005333:Fetus; D006801:Humans; D008353:Mannitol / Q000493:pharmacokinetics
D008353:Mannitol