Integrin receptors and platelet adhesion to synthetic surfaces.
The activation-independent and -dependent integrin receptors--glycoproteins GPIc-IIa (alpha 5-beta 1) and GPIIb-IIIa (alpha IIb-beta 3)--are involved in platelet adhesion and thrombus growth on damaged subendothelium through interactions with fibrinogen, fibronectin, von Willebrand factor, and other adhesive proteins. Because these receptors are used in normal in vivo hemostatic adhesion, they may also have a role for adhesion onto synthetic surfaces in the vasculature. Platelet adhesion in vitro was examined onto Formvar, glass, and four polyurethaneureas with various soft segment chemistries and surface properties. Platelets were pretreated with RGD peptides before and after adhesion. RGD peptide pretreatment inhibited spreading and close contact formation compared to treatment with saline or control RGE peptides, with no observable effect on the number of adherent platelets per area. High-voltage electron microscopy showed abnormally sparse and short microfilament structures with RGD peptide treatment, suggesting an indirect inhibition of actin filament formation. Video-enhanced light microscopy showed a cessation of spreading and a partial reversal of close contacts following RGD peptide application to adherent platelets. Because minimal amounts of plasma proteins are present in column-washed platelet suspensions, and as platelet secretion appeared to be minimal in these experiments, these observations suggest that RGD binding integrin receptors may function in platelet spreading even in the absence of exogenous ligand. As RGD peptides did not affect the numbers of adherent platelets, while producing substantial decreases in the extent of spreading, we suggest that platelet integrins, possibly GPIIb-IIIa, are involved in spreading on synthetic surfaces but not for initial adhesion.
Goodman
S L
SL
Department of Animal Health, University of Wisconsin, Madison 53706.
Cooper
S L
SL
Albrecht
R M
RM
D001792:Blood Platelets / Q000648:ultrastructure; D005898:Glass; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009842:Oligopeptides / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011140:Polyurethanes; D011145:Polyvinyls; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013499:Surface Properties
D016023:Integrins; D009842:Oligopeptides; D011140:Polyurethanes; D011145:Polyvinyls; D011956:Receptors, Cell Surface; C013215:polyvinyl acetate