Thrombospondin binds to monocytes-macrophages and mediates platelet-monocyte adhesion
Abstract:
Thrombospondin (TSP) is a multifunctional platelet glycoprotein synthesized by a variety of cells in culture including monocytes and macrophages. We now report that 125I-TSP binds specifically, saturably, and reversibly to mouse peritoneal macrophages and to cells of the monocyte-like human cell line U937 with dissociation constants of 6.7-14.5 X 10(-8) M and 3-4 X 10(5) binding sites per cell. TSP mediates an adhesive interaction between thrombin-stimulated platelets and both U937 cells and human blood monocytes. Using a sensitive rosetting assay, we found that monocytes were not rosetted by resting platelets whereas greater than 90% were rosetted by thrombin-stimulated platelets. Monoclonal and polyclonal anti-TSP antibodies markedly inhibited rosetting as did TSP itself. Neither control antibodies nor heparin, fibronectin, fibrinogen, nor the fibronectin adhesion tetrapeptide Arg-Gly-Asp-Ser inhibited rosetting. TSP may thus serve as a molecular bridge linking activated platelets with monocytes at sites of early vascular injury. Such interaction may be of critical importance in the regulation of thrombosis and the initiation of atherosclerosis.
Insights
Thrombospondin (TSP) acts as a bridge, connecting activated platelets to monocytes. This interaction is crucial for regulating blood clots and initiating atherosclerosis.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Thrombospondin (TSP) is a multifunctional platelet glycoprotein.
- It is synthesized by various cells, including monocytes and macrophages.
Purpose of the Study:
- To investigate the binding of TSP to macrophages and monocyte-like cells.
- To determine TSP's role in mediating adhesive interactions between platelets and monocytes.
Main Methods:
- Radiolabeled 125I-TSP binding assays on mouse peritoneal macrophages and U937 cells.
- Rosette formation assay using resting and thrombin-stimulated platelets with human blood monocytes.
- Inhibition studies using anti-TSP antibodies, TSP, control antibodies, heparin, fibronectin, fibrinogen, and a fibronectin adhesion tetrapeptide.
Main Results:
- 125I-TSP bound specifically, saturably, and reversibly to macrophages and U937 cells.
- Thrombin-stimulated platelets, but not resting platelets, efficiently rosetted monocytes.
- Anti-TSP antibodies and TSP itself significantly inhibited monocyte-platelet rosetting, while other agents did not.
Conclusions:
- TSP mediates the adhesion between activated platelets and monocytes.
- TSP functions as a molecular bridge linking platelets to monocytes at sites of vascular injury.
- This interaction is potentially critical for thrombosis regulation and atherosclerosis initiation.
Related Concept Videos
Inflammation
Intracellular Signaling Affects Focal Adhesions
Some...
Structure and Function of Platelets
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...
Formation of the Platelet Plug
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...
Clot Retraction and Fibrinolysis
Venous Thrombosis I: Introduction


