Helicobacter pylori urease activates blood platelets through a lipoxygenase-mediated pathway.
The bacterium Helicobacter pylori causes peptic ulcers and gastric cancer in human beings by mechanisms yet not fully understood. H. pylori produces urease which neutralizes the acidic medium permitting its survival in the stomach. We have previously shown that ureases from jackbean, soybean or Bacillus pasteurii induce blood platelet aggregation independently of their enzyme activity by a pathway requiring platelet secretion, activation of calcium channels and lipoxygenase-derived eicosanoids. We investigated whether H. pylori urease displays platelet-activating properties and defined biochemical pathways involved in this phenomenon. For that the effects of purified recombinant H. pylori urease (HPU) added to rabbit platelets were assessed turbidimetrically. ATP secretion and production of lipoxygenase metabolites by activated platelets were measured. Fluorescein-labelled HPU bound to platelets but not to erythrocytes. HPU induced aggregation of rabbit platelets (ED(50) 0.28 microM) accompanied by ATP secretion. No correlation was found between platelet activation and ureolytic activity of HPU. Platelet aggregation was blocked by esculetin (12-lipoxygenase inhibitor) and enhanced approximately 3-fold by indomethacin (cyclooxygenase inhibitor). A metabolite of 12-lipoxygenase was produced by platelets exposed to HPU. Platelet responses to HPU did not involve platelet-activating factor, but required activation of verapamil-inhibitable calcium channels. Our data show that purified H. pylori urease activates blood platelets at submicromolar concentrations. This property seems to be common to ureases regardless of their source (plant or bacteria) or quaternary structure (single, di- or tri-chain proteins). These properties of HPU could play an important role in pathogenesis of gastrointestinal and associated cardiovascular diseases caused by H. pylori.
Wassermann
German E
GE
Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Olivera-Severo
Deiber
D
Uberti
Augusto F
AF
Carlini
Célia R
CR
D016480:Helicobacter pylori / Q000201:enzymology*; D006801:Humans; D058945:Lipoxygenases / Q000378:metabolism*; D015539:Platelet Activation / Q000502:physiology*; D014510:Urease / Q000502:physiology*
D058945:Lipoxygenases; D014510:Urease