Are integrin α₂β₁, glycoprotein Ib and vWf levels correlated with their contributions to platelet adhesion on collagen under high-shear flow?

Abstract

Platelets in flowing blood at high-shear stress are recruited to exposed subendothelial collagen of injured vessels by GPIb–von Willebrand factor (vWf) and integrin α₂β₁ (α₂β₁)–collagen interactions. Platelet adhesion to type I collagen depends mainly on the α₂β₁–collagen interaction and that to type III collagen depends on the GPIb–vWf interaction due to vWf's weak affinity for type I collagen. Contributions of these two interactions would differ depending on expressions of α₂β₁, vWf, or GPIb. We quantitated platelet adhesion to low- and high-density collagen under high-shear flow conditions in the presence of anti-α₂β₁ (Gi9) and anti-GPIb (NNKY5-5) antibodies to determine if their inhibitory effects were correlated with the amounts of α₂β₁, GPIb and vWf. Gi9 inhibition of adhesion to type I collagen was decreased in platelets with more integrin α₂β₁. Gi9 and NNKY5-5 are more inhibitory against adhesion to low-density type III and I, respectively. Higher α₂β₁ expression decreases adhesion to low-density type III and increases Gi9 inhibition of adhesion to high-density type III, suggesting crosstalk between the α₂β₁–collagen and GPIb–vWf interactions in adhesion to type III. Integrin α₂β₁–collagen and GPIb–vWf interactions both contribute to platelet adhesion to collagen under high-shear flow. In adhesion under high-shear stress, the two interactions would compensate for each other, when there is a deficiency in one or the other. The α₂β₁–collagen interaction was also suggested to have an inhibitory effect on platelet adhesion to type III collagen, through a yet undefined mechanism.

• Platelet
• high-shear flow adhesion
• vWf
• collagen
• GPIb
• integrin α₂β₁