title: Are integrin alpha(2)beta(1), 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 alpha(2)beta(1) (alpha(2)beta(1))-collagen interactions. Platelet adhesion to type I collagen depends mainly on the alpha(2)beta(1)-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 alpha(2)beta(1), vWf, or GPIb. We quantitated platelet adhesion to low- and high-density collagen under high-shear flow conditions in the presence of anti-alpha(2)beta(1) (Gi9) and anti-GPIb (NNKY5-5) antibodies to determine if their inhibitory effects were correlated with the amounts of alpha(2)beta(1), GPIb and vWf. Gi9 inhibition of adhesion to type I collagen was decreased in platelets with more integrin alpha(2)beta(1). Gi9 and NNKY5-5 are more inhibitory against adhesion to low-density type III and I, respectively. Higher alpha(2)beta(1) expression decreases adhesion to low-density type III and increases Gi9 inhibition of adhesion to high-density type III, suggesting crosstalk between the alpha(2)beta(1)-collagen and GPIb-vWf interactions in adhesion to type III. Integrin alpha(2)beta(1)-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 alpha(2)beta(1)-collagen interaction was also suggested to have an inhibitory effect on platelet adhesion to type III collagen, through a yet undefined mechanism.
authors.affiliation: Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume-shi, Fukuoka, Japan. smj@lsi.kurume-u.ac.jp
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Jung
authors.forename: Mamiko
authors.initials: M
authors.lastname: Sonoda
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tsuji
authors.forename: Atsuo
authors.initials: A
authors.lastname: Jimi
authors.forename: Shosaku
authors.initials: S
authors.lastname: Nomura
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kanaji
authors.forename: Masaaki
authors.initials: M
authors.lastname: Moroi
mesh_terms: D000293:Adolescent; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D010973:Platelet Adhesiveness / Q000502:physiology*; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D033081:Shear Strength / Q000502:physiology; D013314:Stress, Mechanical; D055815:Young Adult; D014842:von Willebrand Diseases / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D038982:Integrin alpha2beta1; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D014841:von Willebrand Factor