Related Experiment Video
Updated: Jul 16, 2026
10:37
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
CD40L stabilizes arterial thrombi by a beta3 integrin--dependent mechanism
Patrick André1, K S Srinivasa Prasad, Cécile V Denis
1The Center for Blood Research, Harvard Medical School, Boston, Massachusetts, USA.
Nature Medicine
|March 5, 2002
Summary
Platelet CD40L is crucial for arterial thrombus stability and occlusion. Its binding to integrin alphaIIbbeta3 acts as a platelet agonist, essential for effective thrombosis.
Area of Science:
- Immunology
- Hematology
- Cardiovascular Biology
Background:
- CD40L, a TNF superfamily ligand, is vital for immune responses.
- CD40L is expressed on activated platelets and activates endothelium.
- The specific role of platelet CD40L in thrombosis requires further investigation.
Purpose of the Study:
- To elucidate the function of CD40L expressed on activated platelets.
- To determine the role of platelet CD40L in arterial thrombus formation and stability.
- To identify the molecular interactions of CD40L with platelet receptors.
Main Methods:
- Investigated thrombosis in CD40L-deficient mice.
- Administered recombinant soluble CD40L (rsCD40L) with and without the KGD sequence.
- Assessed platelet aggregation under high shear rates.
- Examined binding of rsCD40L to purified integrin alphaIIbbeta3 and activated platelets.
Main Results:
- Absence of CD40L impaired arterial thrombus stability and delayed occlusion.
- rsCD40L restored normal thrombosis, but a KGD-mutant version did not.
- CD40-deficient mice showed normal thrombogenesis, indicating a CD40-independent role for CD40L.
- rsCD40L bound to integrin alphaIIbbeta3 in a beta3-dependent manner, inducing platelet spreading and aggregation.
Conclusions:
- Platelet CD40L is essential for arterial thrombus stability.
- CD40L functions as an alphaIIbbeta3 ligand and a platelet agonist.
- CD40L's interaction with alphaIIbbeta3 is critical for its pro-thrombotic activity.
More Related Videos
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:22Formation of the Platelet Plug
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
01:20Extrinsic and Intrinsic Pathways of Hemostasis
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
01:16Clot Retraction and Fibrinolysis
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.