Impaired mucus-bicarbonate barrier in Helicobacter pylori-infected mice.
To resist the harsh intrinsic milieu, several lines of defense exist in the stomach. The aim of this study was to investigate the effect of the gastric pathogen Helicobacter pylori on these mechanisms in vivo. We used FVB/N mice expressing human alpha-1,3/4-fucosyl transferase (producing Lewis b epitopes) and inoculated with H. pylori 1. Mice were anesthetized with isoflurane or Hypnorm-midazolam, the stomach was exteriorized, and the surface of the corpus mucosa was exposed. Mucus thickness was measured with micropipettes, juxtamucosal pH (pH(jm)) was measured with pH-sensitive microelectrodes, blood flow was measured with laser-Doppler flowmetry, and mRNA levels of the bicarbonate transporter SLC26A9 were quantified with real-time PCR. The increase in mucosal blood flow seen in response to luminal acid (pH 1.5) in control animals (140 +/- 9% of control) was abolished in infected mice. The firmly adherent mucus layer was significantly thinner in infected mice (31 +/- 2 microm) than in control mice (46 +/- 5 microm), and no mucus accumulation occurred in infected mice. pH(jm) decreased significantly more on exposure to luminal acid in infected mice (luminal pH 1.5, pH(jm) 2.4 +/- 0.7) than in control mice (pH(jm) 6.4 +/- 0.5). Despite reduced pH(jm), SLC26A9 mRNA expression was significantly, by increased 1.9-fold, in infected mice. The reduction in pH(jm) by infection with H. pylori might be due to a reduced firmly adherent mucus layer, increased mucus permeability to H(+), and/or inhibition of bicarbonate transport. The upregulation of SLC26A9 in H. pylori-infected epithelium might be a result of continuous inhibition of the transporter, e.g., by ammonium, a H. pylori product, which has been previously shown to inhibit SLC26A9.
Henriksnäs
Johanna
J
Dept. of Medical Cell Biology, Uppsala Univ., PO Box 571, Uppsala SE-751 23, Sweden. Johanna.Henriksnas@medcellbiol.uu.se
Phillipson
Mia
M
Storm
Martin
M
Engstrand
Lars
L
Soleimani
Manoocher
M
Holm
Lena
L
D000818:Animals; D017920:Antiporters / Q000737:chemistry* / Q000378:metabolism*; D001639:Bicarbonates / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism*; D005756:Gastritis / Q000378:metabolism* / Q000382:microbiology; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D000076988:Sulfate Transporters
D017920:Antiporters; D001639:Bicarbonates; C455628:SLC26A9 protein, human; D000076988:Sulfate Transporters