Inhibition of platelet-collagen interaction by propolypeptide of von Willebrand factor.
A collagen-binding glycoprotein was isolated from human platelets using affinity chromatography of immobilized collagen. Based upon characterizations of this protein we confirmed that it was identical to the propolypeptide of von Willebrand factor (pp-vWF), which is also called von Willebrand antigen II. The characteristics we have investigated are molecular weight, existence of carbohydrate chains, and the NH2-terminal amino acid sequence. pp-vWF has strong affinity to collagen and inhibits collagen-induced aggregation of human platelets at a concentration as low as 2 micrograms/ml even in the presence of plasma. This inhibitory effect is specific for collagen-induced aggregation since it does not inhibit aggregation of platelets induced by other agonists such as ADP, arachidonic acid, platelet-activating factor, ionophore A23187, and ristocetin. As pp-vWF is quickly released from platelets upon activation by various agonists, it is possible that pp-vWF functions as a repressor for excess platelet aggregation induced by collagen and constitutes a negative feed-back mechanism. Considering the fact that mature vWF supports platelet adhesion to subendothelium, present observations suggest that the propeptide portion and the mature protein could have opposing effects on hemostasis.
Takagi
J
J
Department of Biological Sciences, Tokyo Institute of Technology, Japan.
Sekiya
F
F
Kasahara
K
K
Inada
Y
Y
Saito
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002417:Cattle; D003094:Collagen / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010974:Platelet Aggregation / Q000187:drug effects*; D011498:Protein Precursors / Q000502:physiology*; D013929:Thromboxane B2 / Q000096:biosynthesis; D014841:von Willebrand Factor / Q000502:physiology*
D006023:Glycoproteins; D011498:Protein Precursors; D014841:von Willebrand Factor; D013929:Thromboxane B2; D003094:Collagen