Von Willebrand factor present in fibrillar collagen enhances platelet adhesion to collagen and collagen-induced platelet aggregation.
We examined the basis of the differences observed between different collagen preparations in their ability to aggregate platelets and support their adhesion under flow. As in previous studies, we found fibrillar collagen to be 10-fold more potent than acid-soluble collagen in inducing platelet aggregation and found that acid-soluble collagen did not support the adhesion of washed platelets under flow. Further, platelets in whole blood adhered to surfaces coated with either fibrillar or acid-soluble collagen, but thrombi formed faster and grew larger on fibrillar collagen. As a possible basis for this difference, we found that fibrillar collagen, but not acid-soluble collagen, contains a substantial quantity of von Willebrand factor (VWF), as demonstrated by enzyme-linked immunosorbent assay and by the ability of fibrillar collagen to support the adhesion of VWF antibody-coated beads and to agglutinate GPIb-IX-V complex-expressing Chinese hamster ovary cells. Supporting a role for VWF in collagen-induced platelet aggregation, aggregation induced by acid-soluble collagen was greatly enhanced by added VWF. Further, platelet aggregation by fibrillar collagen was partially blocked by a GPIbalpha antibody that inhibits the GPIb-VWF interaction. Taken together, these results suggest that much of the difference in prothrombotic potency of different collagens is directly related to their differences in VWF content. This probably accounts for the different conclusions made regarding the relative importance of different direct and indirect collagen receptors in collagen-dependent platelet functions and further emphasizes the close synergistic roles of the GPIb-IX-V complex and the collagen receptors GPVI and alpha2beta1 in supporting platelet adhesion.
Bernardo
A
A
Section of Thrombosis Research, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Bergeron
A L
AL
Sun
C W
CW
Guchhait
P
P
Cruz
M A
MA
López
J A
JA
Dong
J-F
JF
D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D024022:Fibrillar Collagens / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D013927:Thrombosis / Q000209:etiology; D014841:von Willebrand Factor / Q000032:analysis / Q000378:metabolism / Q000502:physiology*
D024022:Fibrillar Collagens; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D014841:von Willebrand Factor; D003094:Collagen