Newly Exposed Membrane Glycoprotein II β (CD41) on Activated Platelets has Higher Affinity for Plasma Fibrinogen that Blocks Anti-CD41 Binding

Bhatt, A; Krishnan, LK

Newly Exposed Membrane Glycoprotein II β (CD41) on Activated Platelets has Higher Affinity for Plasma Fibrinogen that Blocks Anti-CD41 Binding

Date

2015-04

Authors

Bhatt, A

Krishnan, LK

Publisher

International Blood Research Reviews.

Abstract

The density of glycoprotein receptors on platelet membrane is dynamic and increase upon platelet activation by various stimulants to facilitate more ligand binding and functional outcome. Since CD41/61 receptor complex is responsible for platelet to platelet cross-linking, infusion of antagonists/antibodies against these molecules is considered an effective method for inhibiting platelet aggregation in certain clinical conditions. However, binding of anti-CD41 to the platelets stored in bags for transfusion was found to be lower. Probably, upon stimulation the newly exposed receptors may immediately bind fibrinogen and prevent access to the antibody. To prove this hypothesis, binding intensity of FITC-conjugated human fibrinogen to resting and stimulated platelets were compared using flow cytometry. In the presence of plasma fibrinogen, monoclonal antibody binding to the CD41 receptor decreased significantly, both onto the stored and agonistactivated platelets as compared to the resting cells. As compared to ADP-activated platelets, binding of anti-CD41 to thrombin-activated platelets was significantly lower. Variable binding intensity of anti-CD41 to platelets activated by different stimulants observed in this study allowed us to suggest that therapeutic antibodies also may not bind to platelets that are stimulated by strong agonists. Our results signify the importance of validating such antibodies under conditions of stronger activation of platelets. We observed that more platelet microparticles (PMP) were shredded upon in vitro platelet activation by thrombin as compared to induction by ADP. However, fibrinogen did not bind to the shredded microparticles Therefore; PMP in circulation may not take part in pathological thrombus formation.

Keywords

Platelet glycoproteins; flow cytometry; platelet activation; fibrinogen binding; platelet activation markers.

Citation

Bhatt A, Krishnan LK. Newly Exposed Membrane Glycoprotein II β (CD41) on Activated Platelets has Higher Affinity for Plasma Fibrinogen that Blocks Anti-CD41 Binding. International Blood Research Reviews.2015;3(1):1-11