Differential aspects of the glycoprotein Ib-von Willebrand factor axis in human and pig species.
OBJECTIVE
The role of glycoprotein Ib (GPIb) in platelet adhesion to subendothelium is well established in human species. However, the interaction of GPIb and von Willebrand factor (VWF) in a widely used experimental model in thrombosis research, that of the pig, has not been clearly elucidated. We investigated the differences between human and pig species in the GPIb/VWF axis in several ways.


METHODS
Standard aggregometry and perfusion studies with circulating blood were applied to isolated platelets or to blood reconstituted with isolated platelets, VWF and red blood cells from the different species. Platelet aggregation to VWF in the presence of either ristocetin or botrocetin was tested.


RESULTS
Human VWF and ristocetin did not agglutinate pig platelets. However, botrocetin was capable of agglutinating pig platelets. In perfusion studies (800 s(-1), 10 min), washed platelets from both species were suspended in albumin solutions containing human VWF (hVWF) or porcine VWF (pVWF) and red blood cells from the corresponding species. Reconstituted blood with high concentrations of pVWF (> or =0.25 U/mL) caused severe thrombocytopenia during the perfusion procedure when added to human platelets. Nevertheless, lower concentrations (< or =0.1 U/mL) promoted the formation of large aggregates. Under our experimental conditions, hVWF poorly supported pig platelet adhesion.


CONCLUSIONS
In conclusion, pVWF may support human platelet adhesion and even promote aggregation, while hVWF can only partially facilitate pig platelet adhesion. Minimal concentrations of pVWF could facilitate the interaction of human platelets with subendothelium, increasing their adhesive and aggregating capabilities. Understanding the molecular differences of the GPIb-VWF axis in different species may prove useful for developing therapeutic strategies aimed at preventing excessive platelet deposition on damaged vascular surfaces.
Zurbano
M J
MJ
Servicio Hemoterapia/Hemostasia, Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona, Spain. mzurbano@medicina.ub.es
Escolar
G
G
Heras
M
M
Ordinas
A
A
Castillo
R
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001011:Aorta; D003435:Crotalid Venoms / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D010477:Perfusion; D010974:Platelet Aggregation / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D012310:Ristocetin / Q000494:pharmacology; D013552:Swine; D013927:Thrombosis / Q000139:chemically induced; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D003435:Crotalid Venoms; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D012310:Ristocetin; C030961:botrocetin