Upregulation of MUC5AC production and deposition of Lewis determinants by Helicobacter pylori facilitate gastric tissue colonization and the maintenance of infection
Weronika Gonciarz , Maria Walencka , Anthony P. Moran , Krzysztof Hinc , Michał Obuchowski , Magdalena Chmiela
AbstractBackground: Helicobacter pylori bacteria colonize human gastric mucosa, cause chronic inflammation, peptic ulcers and gastric cancer. Colonization is mediated by H. pylori adhesins, which preferentially bind mucin 5 (MUC5AC) and Lewis (Le) determinants. The aim of this study was to evaluate the influence of H. pylori and their components on MUC5AC production and deposition of LeX/LeY in gastric epithelial cells in relation to bacterial adhesion using Caviae porcellus primary gastric epithelial cells and an in vivo model of experimental H. pylori infection in these animals. Methods: MUCA5C and LeX/LeY were induced in vitro by live H. pylori reference strain CCUG 17874 (2 × 107 CFU/ml), H. pylori glycine acid extract (GE), 10 μg/ml; cytotoxin associated gene A (CagA) protein, 1 μl/ml; UreA urease subunit, 5 μg/ml; lipopolysaccharide (LPS) 25 ng/ml and imaged by fluorescence microscopy after anti-MUC5AC or anti-LeX/LeY FITC antibody staining. Bacterial adhesion was imaged by using anti-H. pylori FITC antibodies. The animals were inoculated per os with H. pylori (3 times in 2 days intervals, 1 × 1010 CFU/ml). After 7 or 28 days an infection and inflammation were assessed by histological, serological and molecular methods. Gastric tissue sections of infected and control animals were screend for MUCA5C and LeX, and H. pylori adhesion as above. Results: MUC5AC production and deposition of Lewis determinants, especially LeX were upregulated in the milieu of live H. pylori as well as GE, CagA, UreA or LPS in vitro and in vivo during infection, more effectively in the acute (7 days) than in the chronic (28 days) phase of infection. This was related to enhanced adhesion of H. pylori, which was abrogated by anti-MUC5AC and anti-LeX or anti-LeY antibody treatment. Conclusions: Modulation of MUCA5C production and LeX/LeY deposition in the gastric mucosa by H. pylori can significantly increase gastric tissue colonization during H. pylori infection.
|Journal series||Journal of Biomedical Science, ISSN 1021-7770, (N/A 100 pkt)|
|Publication size in sheets||0.55|
|Keywords in English||MUC5AC, LewisX/Y, H. pylori, Guinea pigs|
|ASJC Classification||; ; ; ; ; ;|
|License||Journal (articles only); published final; ; with publication|
|Score||= 100.0, 15-02-2020, ArticleFromJournal|
|Publication indicators||= 2.000; : 2018 = 1.252; : 2018 = 5.203 (2) - 2018=4.091 (5)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.