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Updated: Aug 15, 2026

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry
Published on: June 5, 2019
ADAM 15 is an adhesion receptor for platelet GPIIb-IIIa and induces platelet activation
Harald Langer1, Andreas E May, Andreas Bültmann
1The Medizinische Klinik III, Universitätsklinikum Tübingen, Eberhard-Karls-Universität Tübingen, Tübingen, Germany.
Abstract:
Cell adhesion and proteolytic matrix degradation are central processes in atherosclerosis. Being a member of the family of ADAMs ("a disintegrin and metalloproteinase"), metargidin (ADAM15) combines a metalloproteinase domain and an RGD aminoacid sequence. We studied the potential role of ADAM15 as an adhesion receptor on endothelial cells and interactions between platelets and ADAM15 with respect to platelet adhesion, activation and thrombus formation. ADAM15 was found to be expressed on cultured endothelial cells (HUVEC). Platelet adhesion to immobilized recombinant ADAM15 was effectively enhanced under both static and high shear rate conditions reaching the maximum level of adhesion to fibrinogen. Consistently, platelet adhesion onto ADAM15 overexpressing endothelial cells was significantly increased. Adhesion to ADAM15 was reduced by blockade of GPIIb-IIIa using neutralizing anti-alpha(IIb)beta3 mAbs (7E3, 2G12), but not by anti-alpha(v)beta3 (LM609). Soluble ADAM15 binds to activated but not to resting GPIIb-IIIa. Moreover, platelets adherent to ADAM15 additionally attracted platelets under high shear rates indicating an initial role of platelet-ADAM15 interactions for thrombus formation. Furthermore, incubation of platelets with soluble ADAM15 showed a dose-dependent increase in secretion of CD62P and CD40L. ADAM15 is expressed on endothelial cells and can serve as an adhesion receptor for platelets via GPIIb-IIIa binding. Platelet adhesion to ADAM15 leads to platelet activation, secretion and promotes thrombus formation. Thus, ADAM15 may represent a novel target for antithrombotic strategies in cardiovascular pathologies.
Insights
Metargidin (ADAM15) acts as an adhesion receptor on endothelial cells, mediating platelet adhesion and activation. This interaction promotes thrombus formation, suggesting ADAM15 as a potential target for antithrombotic therapies in cardiovascular diseases.
Area of Science:
- Biochemistry
- Cell Biology
- Cardiovascular Research
Background:
- Atherosclerosis involves cell adhesion and matrix degradation.
- ADAM15 (a disintegrin and metalloproteinase) possesses metalloproteinase and RGD domains.
- Endothelial cell and platelet interactions are crucial in cardiovascular pathologies.
Purpose of the Study:
- To investigate ADAM15's role as an endothelial cell adhesion receptor.
- To examine ADAM15 interactions with platelets regarding adhesion, activation, and thrombus formation.
Main Methods:
- Studied ADAM15 expression on human umbilical vein endothelial cells (HUVECs).
- Assessed platelet adhesion to immobilized recombinant ADAM15 under static and shear conditions.
- Utilized blocking antibodies against integrins (GPIIb-IIIa, αvβ3).
- Measured platelet secretion markers (CD62P, CD40L) after soluble ADAM15 incubation.
Main Results:
- ADAM15 is expressed on HUVECs.
- Platelet adhesion to ADAM15 was enhanced under static and shear conditions, mediated by GPIIb-IIIa.
- Soluble ADAM15 bound to activated GPIIb-IIIa and induced platelet secretion.
- Adherent platelets on ADAM15 attracted additional platelets, promoting thrombus formation.
Conclusions:
- ADAM15 functions as an endothelial adhesion receptor for platelets via GPIIb-IIIa.
- Platelet adhesion to ADAM15 triggers activation, secretion, and thrombus development.
- ADAM15 presents a potential therapeutic target for antithrombotic strategies in cardiovascular diseases.
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