Platelet size distribution measurements as indicators of shear stress-induced platelet aggregation

Ann Biomed Eng. Nov-Dec 1994;22(6):653-9. doi: 10.1007/BF02368290.

Abstract

The mechanisms underlying shear stress-induced platelet aggregation (SIPA) were investigated by measuring changes in the platelet size distributions resulting from the exposure of human platelet-rich plasma (PRP) to well-defined shear stresses in a modified viscometer. Exposure of PRP to a shear stress of 100 dyne/cm2 for 1 min at 37 degrees C resulted in the loss of single platelets, an overall shift in the distribution to larger particle sizes, and the generation of platelet fragments. Treatment of PRP prior to shearing with a monoclonal antibody directed against platelet glycoprotein (GP) IIb-IIIa (integrin alpha IIb beta 3) at a concentration that completely inhibited ADP-induced platelet aggregation also inhibited SIPA. Furthermore, incubation of PRP with a recombinant fragment of von Willebrand factor (vWF) that abolishes ristocetin-induced platelet agglutination significantly inhibited but did not eliminate SIPA. Pretreatment of PRP with the tetrapeptides RGDS or RGDV, which constitute the GP IIb-IIIa peptide recognition sequences on fibrinogen and vWF, almost completely blocked platelet aggregation at 100 dyne/cm2, whereas the negative control peptide RGES had no discernible effect. Finally, incubation of PRP with a monoclonal antibody directed against the platelet vitronectin receptor (integrin alpha v beta 3) did not affect SIPA. These results indicate that both GP IIb-IIIa and GP Ib, the latter through its interaction with vWF, are required for SIPA at 100 dyne/cm2; that the interaction of GP IIb-IIIa with its adhesive ligands under shear stress can be inhibited by RGD-containing peptides; and that the vitronectin receptor on platelets, which shares the same beta 3 subunit as GP IIb-IIIa, plays no role in SIPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • Blood Platelets / cytology*
  • Blood Platelets / metabolism
  • Cell Size
  • Glycoproteins / metabolism
  • Humans
  • Integrins / metabolism
  • Platelet Aggregation*
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptors, Cytoadhesin / metabolism
  • Receptors, Vitronectin
  • Rheology
  • Stress, Mechanical
  • Vitronectin
  • von Willebrand Factor / metabolism

Substances

  • Antibodies, Monoclonal
  • Glycoproteins
  • Integrins
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptors, Cytoadhesin
  • Receptors, Vitronectin
  • Vitronectin
  • von Willebrand Factor