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Protein disulphide isomerase mediates platelet aggregation and secretion
1Department of Medicine, State University of New York, Health Science Center at Brooklyn, 11203, USA.
British Journal of Haematology
|March 23, 1999
Summary
Protein disulphide isomerase (PDI) on platelet surfaces is crucial for platelet aggregation and secretion. Inhibiting PDI blocks platelet activation, revealing its role in glycoprotein IIbIIIa receptor function.
Area of Science:
- Biochemistry
- Hematology
- Molecular Biology
Background:
- Platelet surface thiols and disulphides are vital for platelet function.
- Disulphide bond reduction exposes and activates the glycoprotein (GP) IIbIIIa receptor.
- Protein disulphide isomerase (PDI) is present and active on the platelet surface.
Purpose of the Study:
- To investigate the role of PDI in platelet aggregation and secretion.
- To determine if PDI mediates the activation of the GP IIbIIIa receptor.
Main Methods:
- Utilized rabbit anti-PDI IgG (and its Fab fragments) to inhibit PDI.
- Employed a competing substrate (scrambled ribonuclease A) and a PDI inhibitor (bacitracin).
- Assessed platelet responses using aggregation assays, secretion measurements, and flow cytometry with PAC-1 antibody for activated GPIIbIIIa.
Main Results:
- Anti-PDI Fab fragments inhibited platelet responses to ADP and collagen.
- Scrambled ribonuclease A inhibited platelet aggregation and secretion.
- Bacitracin primarily affected the second phase of aggregation and associated secretion.
- Anti-PDI Fab fragments inhibited GPIIbIIIa activation when added before, but not after, platelet activation.
Conclusions:
- Protein disulphide isomerase (PDI) plays a mediating role in platelet aggregation and secretion.
- PDI activation of the glycoprotein IIbIIIa receptor is demonstrated.
- PDI is identified as a key enzyme regulating platelet activation pathways.