Helicobacter pylori binds von Willebrand factor and interacts with GPIb to induce platelet aggregation.
OBJECTIVE
Clinical studies have suggested an association between cardiovascular disease and infection with Helicobacter pylori. We examined the effect of H. pylori on platelets and the mechanism of the interaction.


METHODS
Three of 5 strains of H. pylori induced platelet aggregation with a lag time of 5 +/- 2 minutes that was independent of the toxigenic genes cagA and vacA. Aggregation was inhibited completely by aspirin and a glycoprotein (GP) IIb/IIIa antagonist. Aggregation also was inhibited by monoclonal antibodies that prevented the von Willebrand factor (vWF) interaction with GPIb. vWF-coated H. pylori bound to cells transfected with GPIbalpha but not to mock transfected cells and this was inhibited by an antibody to GPIb.


RESULTS
The interaction with platelets appeared to be mediated by vWF because platelet aggregation was blocked by an antibody to vWF. Moreover, a strain of H. pylori that induced platelet aggregation bound vWF to a greater extent than a nonaggregating strain. Aggregation also required IgG and could be inhibited by an antibody to the platelet IgG receptor (FcgammaRIIA).


CONCLUSIONS
Some strains of H. pylori induce platelet activation mediated by H. pylori-bound vWF interacting with GPIb, and supported by IgG. These platelet-H. pylori interactions may contribute to the pathogenesis of H. pylori-associated peptic ulcer disease and to the association between H. pylori infection and cardiovascular disease, whereas local platelet effects may contribute to the pathogenesis of H. pylori-associated peptic ulcer disease.
Byrne
Michael F
MF
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland.
Kerrigan
Steven W
SW
Corcoran
Paul A
PA
Atherton
John C
JC
Murray
Frank E
FE
Fitzgerald
Desmond J
DJ
Cox
Dermot M
DM
D000818:Animals; D000907:Antibodies, Bacterial / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D010437:Peptic Ulcer / Q000209:etiology; D010974:Platelet Aggregation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology*; D014841:von Willebrand Factor / Q000502:physiology*
D000907:Antibodies, Bacterial; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor