title: Platelet adhesion to decorin but not collagen I correlates with the integrin α2 dimorphism E534K, the basis of the human platelet alloantigen (HPA)-5 system.
abstract: A single nucleotide polymorphism in the integrin α2 gene ITGA2 (rs1801106; G1600A) creates the non-conservative amino acid substitution E534K, the basis of the human platelet alloantigen system HPA-5. Yet HPA-5 alleles do not influence binding of α2β1 to its primary ligand collagen I, and the effect of HPA-5 on platelet function has not been determined. We used a direct platelet adhesion assay to evaluate whether differential inheritance of HPA-5 alleles influences platelet adhesion to collagen I or an alternative ligand, decorin. Platelets from donors bearing one or more minor allele HPA-5b showed attenuated adhesion to purified decorin but not collagen I. Adhesion to decorin was significantly inhibited by human alloantibodies specific for HPA-5a but not by the collagen I sequence GFOGER or α2-specific inhibitory monoclonal antibodies. The minor allele 534K attenuates platelet adhesion to decorin but not collagen I, providing the first evidence of a functional effect of HPA-5 alleles.
authors: CHOC Children’s Hospital, University of California-Irvine, Hematology Research, Orange, CA 92868, USA. tkunicki@choc.org
authors: Thomas J
authors: TJ
authors: Kunicki
authors: Shirley A
authors: SA
authors: Williams
authors: Daniel
authors: D
authors: Diaz
authors: Richard W
authors: RW
authors: Farndale
authors: Diane J
authors: DJ
authors: Nugent
mesh_terms: D000328:Adult; D016824:Antigens, Human Platelet / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001792:Blood Platelets / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism*; D058575:Decorin / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D010973:Platelet Adhesiveness / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: C071092:5a alloantigen, human; C055973:5b alloantigen, human; D016824:Antigens, Human Platelet; D024042:Collagen Type I; D058575:Decorin; D039421:Integrin alpha2