Synthetic RGDS-containing peptides of von Willebrand factor inhibit platelet adhesion to collagen.
We compared the effect of a synthetic dodecapeptide of residues 400-411 of the gamma chain of fibrinogen (gamma Fg 400-411) and of three synthetic peptides (15 to 18 aminoacids), of human von Willebrand Factor (vWF), containing the 1744-1747 Arg-Gly-Asp-Ser (RGDS) sequence, upon platelet adhesion to collagen in flowing blood. Both types of peptides are known to inhibit the binding of adhesive proteins to platelet membrane glycoprotein IIb/IIIa (GPIIb/IIIa). Collagen was coated onto plastic cover slips and exposed in parallel-plate perfusion chambers to reconstituted human blood at various shear rates for 5 min at 37 degrees C. At a shear rate of 2,600 s-1, RGDS peptides inhibited platelet adhesion to collagen in a dose-dependent manner and appeared to be more potent inhibitors than the gamma Fg 400-411 on a molar basis. No synergetic effect between RGDS and gamma Fg 400-411 peptides was observed. These results suggest that the RGDS peptides affect adhesion by inhibiting the GPIIb/IIIa-vWF interaction and confirm the involvement of this platelet receptor in vWF-mediated platelet adhesion to collagen at high shear rate.
Fressinaud
E
E
Laboratoire d'Hémostase, CDTS, Angers, France.
Girma
J P
JP
Sadler
J E
JE
Baumgartner
H R
HR
Meyer
D
D
D000595:Amino Acid Sequence; D003094:Collagen; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000502:physiology*; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000502:physiology*; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000737:chemistry*
D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D003094:Collagen; C046617:arginyl-glycyl-aspartyl-serine