title: Vacuolating cytotoxin A is associated with increased thrombin generation in gastric mucosa.
abstract: BACKGROUND
  Activation of the coagulation system is a critical response for both the repair of tissue injury and the host defense against microbial pathogens. Activation of the coagulation cascade culminates with the generation of thrombin. In vitro studies have shown that thrombin protects gastric epithelial cells from injury. The present study was undertaken to assess in vivo the relationship between gastric intramucosal generation of thrombin and Helicobacter pylori infection.
  
  
  METHODS
  This study comprised 59 patients with gastroduodenal disorders. There were 27 patients with H. pylori infection (Hp+), 14 without it (Hp-), and 18 patients with cured H. pylori infection (Hp c). The gastric intramucosal concentrations of thrombin-antithrombin complex (TAT), epidermal growth factor (EGF), prostaglandin E2 (PGE2), and vacuolating cytotoxin A (VacA) were measured by specific immunoassays.
  
  
  RESULTS
  The level of TAT was significantly increased in patients with Hp+ compared to Hp- and Hp c. The levels of TAT, EGF and PGE2 were higher in VacA (+) patients than in those with VacA (-). VacA induced significant expression of tissue factor in gastric epithelial cells in vitro. The gastric intramucosal level of VacA antigen was proportionally and significantly correlated with TAT, EGF and PGE2 in Hp+ patients. The level of TAT was proportionally and significantly correlated with EGF in Hp+ patients but not in Hp- and HP c patients.
  
  
  CONCLUSIONS
  These results showed that VacA produced by H. pylori is associated with increased thrombin generation, and that thrombin may play a protective role in H. pylori-associated gastroduodenal disorders.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mie University School of Medicine, Edobashi 2-174, Tsu city, Mie 514-8507, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Esteban Cesar
authors.initials: EC
authors.lastname: Gabazza
authors.forename: Ichiro
authors.initials: I
authors.lastname: Imoto
authors.forename: Roger F L
authors.initials: RF
authors.lastname: James
authors.forename: Toshiya
authors.initials: T
authors.lastname: Hirayama
authors.forename: Akihiro
authors.initials: A
authors.lastname: Wada
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Horiki
authors.forename: Misaki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inoue
authors.forename: Mikito
authors.initials: M
authors.lastname: Kuroda
authors.forename: Ayumi
authors.initials: A
authors.lastname: Ogura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Taguchi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yano
authors.forename: Osamu
authors.initials: O
authors.lastname: Taguchi
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Adachi
mesh_terms: D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism*; D005767:Gastrointestinal Diseases / Q000382:microbiology*; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori; C046193:antithrombin III-protease complex; D004815:Epidermal Growth Factor; D000990:Antithrombin III; D010447:Peptide Hydrolases; D013917:Thrombin; D015232:Dinoprostone