Related Experiment Videos
Red cell ICAM-4 is a novel ligand for platelet-activated alpha IIbbeta 3 integrin
Patricia Hermand1, Pierre Gane, Martine Huet
1INSERM U76, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75015 Paris, France.
The Journal of Biological Chemistry
|December 13, 2002
Summary
Intercellular adhesion molecule-4 (ICAM-4) on red blood cells binds to activated platelets via the alpha(IIb)beta(3) integrin. This interaction, crucial for hemostasis and thrombosis, identifies ICAM-4 as a key platelet ligand on RBCs.
Area of Science:
- Hematology
- Cell Biology
- Immunology
Background:
- Intercellular adhesion molecule-4 (ICAM-4), also known as the LW blood group glycoprotein, is an erythroid-specific membrane protein.
- ICAM-4 interacts with integrins, suggesting a role in cell adhesion events like hemostasis and thrombosis.
Purpose of the Study:
- To investigate the interaction between ICAM-4 and platelets.
- To identify the specific receptor on platelets that binds to ICAM-4.
Main Methods:
- Cell adhesion assays using immobilized red blood cells (RBCs), platelets, and ICAM-Fc fusion proteins.
- Analysis of interactions with normal and patient-derived cells, including those expressing alpha(IIb)beta(3) integrin.
- Inhibition studies using monoclonal antibodies and synthetic peptides.
Main Results:
- The alpha(IIb)beta(3) integrin (platelet fibrinogen receptor) was identified as the receptor for ICAM-4 on activated platelets.
- Platelet adhesion to ICAM-4 was inhibited by antibodies against beta(3)-chain and alpha(IIb)beta(3) integrin, and by ICAM-4 itself.
- Platelet adhesion was significantly reduced in patients with Glanzmann's thrombasthenia, who lack functional alpha(IIb)beta(3).
- The binding site on ICAM-4 involves the first two Ig domains, potentially including the G65-V74 sequence.
Conclusions:
- ICAM-4 is the first identified red blood cell protein that acts as a ligand for platelets.
- This RBC-platelet interaction mediated by ICAM-4 and alpha(IIb)beta(3) integrin has significant physiological implications for hemostasis and thrombosis.