Related Experiment Video

Updated: Aug 23, 2026

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry
04:32

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry

Published on: June 5, 2019

Release of soluble CD40L from platelets is regulated by glycoprotein IIb/IIIa and actin polymerization

Mark I Furman1, Lori A Krueger, Matthew D Linden

  • 1Center for Platelet Function Studies, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.

Journal of the American College of Cardiology
|June 15, 2004
PubMed

Insights

Glycoprotein IIb/IIIa antagonists inhibit the release of soluble CD40L (sCD40L) from activated platelets, potentially reducing its prothrombotic effects. This release is regulated by GP IIb/IIIa, actin polymerization, and matrix metalloproteinases.

Area of Science:

  • Hematology
  • Immunology
  • Pharmacology

Background:

  • CD40L is a proinflammatory and prothrombotic ligand.
  • It belongs to the tumor necrosis factor superfamily.
  • CD40L plays a role in inflammatory and thrombotic processes.

Purpose of the Study:

  • To investigate the effects of glycoprotein (GP) IIb/IIIa antagonists on CD40L translocation and release.
  • To examine the role of other inhibitors in CD40L regulation.
  • To understand the mechanisms of soluble CD40L (sCD40L) release from platelets.

Main Methods:

  • Platelet surface CD40L measured by flow cytometry.
  • sCD40L quantified using enzyme-linked immunosorbent assay (ELISA).
  • Effects of GP IIb/IIIa antagonists, ethylenediaminetetraacetic acid, cytochalasin D, and GM6001 were assessed.

Main Results:

  • GP IIb/IIIa antagonists did not inhibit CD40L translocation but dose-dependently inhibited sCD40L release.
  • sCD40L release was reduced in Glanzmann platelets, deficient in GP IIb/IIIa.
  • Cytochalasin D and GM6001 inhibited sCD40L release but not translocation.

Conclusions:

  • GP IIb/IIIa antagonists inhibit sCD40L release from activated platelets.
  • sCD40L release is regulated by GP IIb/IIIa, actin polymerization, and matrix metalloproteinases.
  • GP IIb/IIIa antagonists may mitigate the proinflammatory and prothrombotic effects of sCD40L.
Abstract

More Related Videos

Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation08:30

Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation

Published on: August 14, 2017

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers05:43

An In Vitro Assay to Study Platelet Migration Using RGD-Functionalized Avidin-Biotin Tethers

Published on: November 8, 2024

Related Concept Videos

Formation of the Platelet Plug01:22

Formation 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...
Structure and Function of Platelets01:18

Structure and Function of Platelets

The cell fragments known as platelets are disc-shaped, with an average diameter of about 3 μm and a thickness of roughly 1 μm. They play a crucial role in the body's vascular clotting system, which also involves plasma proteins, blood cells, and blood vessel tissues.
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000 platelets, with...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular 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...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Clot Retraction and Fibrinolysis01:16

Clot 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.
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...