title: Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (alpha 2 beta 1-integrin).
abstract: Platelet adhesion to fibrillar collagens (types I, II, III, and V) and nonfibrillar collagens (types IV, VI, VII, and VIII) was investigated in the presence of physiologic concentrations of divalent cations under conditions of stasis and flow. Under static conditions, platelet adhesion was observed to collagen types I through VII but not to type VIII. Under flow conditions, platelet adhesion to collagen types I, II, III, and IV was almost independent of shear rates above 300/s. Collagen type V was nonadhesive. Platelet adhesion to collagen type VI was shear rate-dependent and optimal at a rate of 300/s. Collagen types VII and VIII showed minor reactivity and supported platelet adhesion only between shear rates 100 to 1,000/s. Monoclonal antibody (MoAb) 176D7, directed against platelet membrane glycoprotein Ia (GPIa; very late antigen [VLA]-alpha 2 subunit), completely inhibited platelet adhesion to all collagens tested, under conditions of both stasis and flow. Platelet adhesion to collagen type III at shear rate 1,600/s was only inhibited for 85%. The concentration of antibody required for complete inhibition of platelet adhesion was dependent on the shear rate and the reactivity of the collagen. An MoAb directed against GPIIa (VLA-beta subunit) partially inhibited platelet adhesion to collagen. These results show that GPIa-IIa is a major and universal platelet receptor for eight unique types of collagen.
authors.affiliation: Department of Haematology, University Hospital Utrecht, The Netherlands.
authors.forename: E U
authors.initials: EU
authors.lastname: Saelman
authors.forename: H K
authors.initials: HK
authors.lastname: Nieuwenhuis
authors.forename: K M
authors.initials: KM
authors.lastname: Hese
authors.forename: P G
authors.initials: PG
authors.lastname: de Groot
authors.forename: H F
authors.initials: HF
authors.lastname: Heijnen
authors.forename: E H
authors.initials: EH
authors.lastname: Sage
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: L
authors.initials: L
authors.lastname: McKeown
authors.forename: H R
authors.initials: HR
authors.lastname: Gralnick
authors.forename: J J
authors.initials: JJ
authors.lastname: Sixma
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D003094:Collagen / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology*; D008854:Microscopy, Electron; D010973:Platelet Adhesiveness; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D011485:Protein Binding; D012212:Rheology
chemical_list: D000911:Antibodies, Monoclonal; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D003094:Collagen