PMID- 8259558
OWN - NLM
STAT- MEDLINE
DCOM- 19940119
LR  - 20161123
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 70
IP  - 3
DP  - 1993 Sep 1
TI  - Platelet aggregation on extracellular matrix: effect of a recombinant 
      GPIb-binding fragment of von Willebrand factor.
PG  - 522-6
AB  - Platelets in whole blood incubated on extracellular matrix (ECM) produced by 
      bovine corneal endothelial cells under oscillatory flow conditions demonstrate 
      extensive aggregate formation. Since both platelet-subendothelium and 
      platelet-platelet interactions are mediated by von Willebrand factor (vWF), we 
      used this system to examine the effect of a recombinant GPIb-binding fragment of 
      vWF (designated RG12986), comprising residues 445-733 of the native vWF subunit, 
      on platelet reactivity with ECM. The seven cysteines present in the RG12986 
      fragment were reduced and alkylated in order to achieve a monomeric conformation. 
      The recombinant vWF fragment binds to unstimulated platelets in the absence of 
      exogenous modulators. When added to platelet-rich plasma, it inhibits 
      ristocetin-induced platelet agglutination. Binding of 51Cr-labeled platelets in 
      reconstituted whole blood to ECM was inhibited by RG12986 in a dose dependent and 
      saturable manner, with IC50 of 4 microM and maximal inhibition (about 70%) at 6 
      microM. Scanning electron microscope (SEM) analysis showed that addition of 
      RG12986 to whole blood significantly inhibited platelet aggregation on ECM. The 
      extent of inhibition observed with RG12986 at a final concentration of 4 microM 
      was similar to that obtained with the cell adhesion peptide RGDS at the 
      concentration of 0.1 mM. The ability of the RG12986 fragment to inhibit platelet 
      aggregation on ECM is in agreement with the concept that blockade of vWF-GPIb 
      interaction may inhibit further events leading to activation of the glycoprotein 
      IIb/IIIa (GPIIb/IIIa) complex and subsequent thrombus formation.
FAU - Dardik, R
AU  - Dardik R
AD  - National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel.
FAU - Ruggeri, Z M
AU  - Ruggeri ZM
FAU - Savion, N
AU  - Savion N
FAU - Gitel, S
AU  - Gitel S
FAU - Martinowitz, U
AU  - Martinowitz U
FAU - Chu, V
AU  - Chu V
FAU - Varon, D
AU  - Varon D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Chromium Radioisotopes)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptide Fragments)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Platelet Membrane Glycoproteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (von Willebrand Factor)
RN  - 0 (von Willebrand factor (445-733))
RN  - 1404-55-3 (Ristocetin)
RN  - AC6UDA2MFC (arginyl-glycyl-aspartyl-serine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Chromium Radioisotopes
MH  - Extracellular Matrix/*drug effects
MH  - Hemagglutination/drug effects
MH  - Humans
MH  - Molecular Sequence Data
MH  - Oligopeptides/pharmacology
MH  - Peptide Fragments/*metabolism
MH  - Platelet Adhesiveness/drug effects
MH  - Platelet Aggregation/*drug effects
MH  - Platelet Aggregation Inhibitors/pharmacology
MH  - Platelet Membrane Glycoproteins/*antagonists & inhibitors
MH  - Protein Binding
MH  - Recombinant Proteins/pharmacology
MH  - Ristocetin/antagonists & inhibitors
MH  - von Willebrand Factor/*metabolism
EDAT- 1993/09/01 00:00
MHDA- 1993/09/01 00:01
CRDT- 1993/09/01 00:00
PHST- 1993/09/01 00:00 [pubmed]
PHST- 1993/09/01 00:01 [medline]
PHST- 1993/09/01 00:00 [entrez]
PST - ppublish
SO  - Thromb Haemost. 1993 Sep 1;70(3):522-6.