title: Platelet adhesion to fibronectin in flow: the importance of von Willebrand factor and glycoprotein Ib.
abstract: We describe glycoprotein (GP) Ib as a mediator of adhesion to fibronectin, specifically in flow. A monoclonal antibody (MoAb) directed to the von Willebrand factor (vWF)-binding site on this receptor or the absence of this receptor on the platelet membrane, in the case of a patient with the Bernard-Soulier syndrome, reduced platelet coverage to fibronectin to approximately 30% of the control value. A MoAb directed to the GP Ib-binding site on vWF showed a similar effect. With washed platelets in the absence of plasma vWF, the inhibitory effect of the anti-GP Ib antibody was the same as with whole blood. No inhibition with the anti-GP Ib antibody was observed when we used blood from patients with severe von Willebrand disease (vWD) or from a patient with vWD type I (platelet low). Addition of vWF to vWD blood resulted in restoration of adhesion. Immunoelectron microscopy on platelets adhering to fibronectin showed that GP Ib was homogeneously distributed over the entire surface of the platelet. vWF was present at the central zone and the edges of the platelet and at the basal interface between the platelet and the fibronectin surface. No direct binding of vWF to fibronectin could be demonstrated. These data indicate that GP Ib-mediated adhesion to fibronectin fully depends on vWF and that normal levels of plasma or platelet vWF are sufficient for optimal adhesion to fibronectin. The data suggest that the presence of platelets during perfusion is a prerequisite for vWF to support platelet adhesion to fibronectin.
authors.affiliation: Department of Haematology, University Hospital Utrecht, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Beumer
authors.forename: H F
authors.initials: HF
authors.lastname: Heijnen
authors.forename: M J
authors.initials: MJ
authors.lastname: IJsseldijk
authors.forename: E
authors.initials: E
authors.lastname: Orlando
authors.forename: P G
authors.initials: PG
authors.lastname: de Groot
authors.forename: J J
authors.initials: JJ
authors.lastname: Sixma
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D001606:Bernard-Soulier Syndrome / Q000097:blood; D001792:Blood Platelets / Q000737:chemistry / Q000648:ultrastructure; D048429:Cell Size; D005353:Fibronectins / Q000378:metabolism*; D018056:Hemorheology; D006801:Humans; D046911:Macromolecular Substances; D008954:Models, Biological; D010973:Platelet Adhesiveness / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology*; D011485:Protein Binding; D017469:Receptors, Fibronectin / Q000502:physiology*; D014841:von Willebrand Factor / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D005353:Fibronectins; D046911:Macromolecular Substances; D019038:Platelet Glycoprotein GPIb-IX Complex; D017469:Receptors, Fibronectin; D014841:von Willebrand Factor