title: Adhesion of platelets to surface-bound fibrinogen under flow.
abstract: After platelet activation, fibrinogen mediates platelet-platelet interactions leading to platelet aggregation. In addition, fibrinogen can also function as a cell adhesion molecule, providing a substratum for adhesion of platelets and endothelial cells. In this report, we studied the adhesion of platelets to surface-immobilized fibrinogen under flow in different shear rates. Heparinized whole blood containing mepacrine-labeled platelets was perfused for two minutes at various wall shear rates from 250 to 2,000 s-1 in a parallel plate flow chamber. The number of adherent fluorescent platelets was quantitated every 15 seconds with an epifluorescent videomicroscope and digital image processing system. When compared with platelet adhesion and aggregation seen on glass surfaces coated with type I bovine collagen, a significant increase in platelet adhesion was observed on immobilized fibrinogen up to wall shear rates of 800 s-1. The adherent platelets formed a single layer on fibrinogen-coated surfaces. Under identical conditions, no significant adhesion was observed on fibronectin- or vitronectin-coated surfaces. Although platelet adhesion to collagen was substantially inhibited by the platelet inhibitors prostaglandin E1 and theophylline, these inhibitors had no effect on platelet adhesion to fibrinogen. Platelets adhered to recombinant homodimeric wild-type (gamma 400-411) fibrinogen, but not to the recombinant homodimeric gamma' variant of fibrinogen. Platelet adhesion to recombinant fibrinogen with RGD to RGE mutations at positions alpha 95-97 and alpha 572-574 was similar to that with plasma-derived fibrinogen. These results show that platelets adhere to fibrinogen-coated surfaces under moderate wall shear rates, that the interaction is mediated by the fibrinogen 400-411 sequence at the carboxy-terminus of the gamma chain, and that the interaction is independent of platelet activation and the RGD sequences in the alpha chain.
authors.affiliation: Cox Laboratory for Biomedical Engineering, Rice University, Houston, TX, USA.
authors.forename: T N
authors.initials: TN
authors.lastname: Zaidi
authors.forename: L V
authors.initials: LV
authors.lastname: McIntire
authors.forename: D H
authors.initials: DH
authors.lastname: Farrell
authors.forename: P
authors.initials: P
authors.lastname: Thiagarajan
mesh_terms: D000527:Alprostadil / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003094:Collagen / Q000378:metabolism; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism*; D018056:Hemorheology; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010973:Platelet Adhesiveness / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D005340:Fibrinogen; D003094:Collagen; D013806:Theophylline; D000527:Alprostadil