Vacuolating cytotoxin A is associated with increased thrombin generation in gastric mucosa.
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.
Suzuki
Yuko
Y
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mie University School of Medicine, Edobashi 2-174, Tsu city, Mie 514-8507, Japan.
Gabazza
Esteban Cesar
EC
Imoto
Ichiro
I
James
Roger F L
RF
Hirayama
Toshiya
T
Wada
Akihiro
A
Horiki
Noriyuki
N
Nakamura
Misaki
M
Inoue
Hiroyuki
H
Kuroda
Mikito
M
Ogura
Ayumi
A
Taguchi
Yukiko
Y
Yano
Yutaka
Y
Taguchi
Osamu
O
Suzuki
Koji
K
Adachi
Yukihiko
Y
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
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