Collagen-type specificity of glycoprotein VI as a determinant of platelet adhesion

• Published in: Platelets (Edinburgh) 2008-01, Vol.19 (1), p.32-42
• Main Authors: Jung, Stephanie M., Takemura, Yukitoshi, Imamura, Yasutada, Hayashi, Toshihiko, Adachi, Eijiro, Moroi, Masaaki
• Format: Article
• Language: English
• Subjects: Adhesion; Animals; Blood Platelets - chemistry; Blood Platelets - metabolism; Cattle; collagen; collagen receptor; Fibrillar Collagens - chemistry; Fibrillar Collagens - metabolism; glycoprotein VI; Humans; Integrin alpha2beta1 - chemistry; Integrin alpha2beta1 - metabolism; Kinetics; platelet; Platelet Adhesiveness - physiology; Platelet Membrane Glycoproteins - chemistry; Platelet Membrane Glycoproteins - genetics; Platelet Membrane Glycoproteins - metabolism; Protein Binding - physiology; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Substrate Specificity - physiology
• ISSN: 0953-7104; 1369-1635
• DOI: 10.1080/09537100701609027

Of the two physiologically important platelet collagen receptors, glycoprotein (GP) VI is the receptor responsible for platelet activation. However, its reactivities towards different types of vascular collagen have not been directly and quantitatively analysed with collagen preparations of defined composition, although the other major platelet collagen receptor integrin α2β1 was shown to react with collagen types I-VI and VIII under either static or flow conditions. We analysed the collagen type specificity of GPVI binding to identify the physiological contribution of the various vascular collagens and how platelet reactivity towards the various collagens may be affected by fibril size. We used two methods to analyse the binding of recombinant GPVI (GPVI-Fc2) to different types of bovine collagen: binding to collagen microparticles in suspension and binding to immobilized collagen. GPVI-Fc2 bound to type I-III collagens that can form large fibrils, but not to type V that only forms small fibrils. The apparent GPVI binding to types IV and V could be ascribed to type I collagen that was a contaminant in each of these preparations. Kinetic analyses of the binding data showed that type III collagen fibrils have both a higher Kd and Bmax than types I and II. Flow adhesion studies demonstrated that type III collagen supports the formation of larger platelet aggregates than type I. Our present results suggest that the physiological importance of type III collagen is to induce thrombus formation. Furthermore, these studies indicate that GPVI mainly binds to collagen types that can form large collagen fibrils.