Reconstitution of adhesive properties of human platelets in liposomes carrying both recombinant glycoproteins Ia/IIa and Ibα under flow conditions: Specific synergy of receptor-ligand interactions

Takako Nishiya, Mie Kainoh, Mitsuru Murata, Makoto Handa, Yasuo Ikeda

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Liposomes carrying both recombinant glycoprotein Ia/IIa (rGPIa/IIa) and Ibα (rGPIbα) (rGPIa/IIa-Ibα-liposomes) instantaneously and irreversibly adhered to the collagen surface in the presence of soluble von Willebrand factor (VWF) at high shear rates, in marked contrast with translocation of liposomes carrying rGPIbα alone on the VWF surface. In the absence of soluble VWF, the adhesion of rGPIa/IIa-Ibα-liposomes to the collagen surface decreased with increasing shear rates, similar to liposomes carrying rGPIa/IIa alone. While adhesion of liposomes with exofacial rGPIa/IIa and rGPIbα densities of 2.17 × 103 and 1.00 × 104 molecules per particle, respectively, was efficient at high shear rates, reduction in rGPIbα density to 5.27 × 103 molecules per particle resulted in decreased adhesion even in the presence of soluble VWF. A 50% reduction in the exofacial rGPIa/IIa density resulted in a marked decrease in the adhesive ability of the liposomes at all shear rates tested. The inhibitory effect of antibody against GPIbα (GUR83-35) on liposome adhesion was greater at higher shear rates. Further, the anti-GPIa antibody (Gi9) inhibited liposome adhesion more than GUR83-35 at all shear rates tested. These results suggest that the rGPIa/IIa-collagen interaction dominates the adhesion of rGPIa/IIa-Ibα-liposomes to the collagen surface at low shear rates, while the rGPIa/IIa-collagen and rGPIbα-VWF interaction complements each other, and they synergistically provide the needed functional integration required for liposome adhesion at high shear rates. This study thus has confirmed for the first time the proposed mechanisms of platelet adhesion to the collagen surface under flow conditions using the liposome system.

Original languageEnglish
Pages (from-to)136-142
Number of pages7
JournalBlood
Volume100
Issue number1
DOIs
Publication statusPublished - 2002 Jul 1

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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