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Prepublished online as a Blood First Edition Paper on February 27, 2003; DOI 10.1182/blood-2002-11-3483.

Submitted November 19, 2002
Accepted February 14, 2003
Involvement of a CD47-dependent pathway in platelet adhesion on inflamed vascular endothelium under flow
Patricia Lagadec, Olivier Dejoux, Michel Ticchioni, Francoise Cottrez, Mette Johansen, Eric J Brown, and Alain Bernard*
Laboratory of Immunology, INSERM, Unite 343, Nice, France
Center for Host/Pathogen Interactions, University of California, San Francisco, CA, USA
* Corresponding author; email: abernard{at}unice.fr.
Resting platelet adhesion to inflammatory vascular endothelium is thought to play a causal role in secondary thrombus formation or microcirculatory disturbance after vessel occlusion. However, while adhesion receptors involved in platelet/matrix interactions have been extensively studied, the molecular mechanisms involved in platelet/endothelium interactions are incompletely characterized and have been mainly studied under static conditions. Using human platelets or platelets from wild type and CD47-/- mice in whole blood, we demonstrated that at low shear rate, CD47 expressed on human and mouse platelets significantly contributes to platelet adhesion on TNF- -stimulated vascular endothelial cells. Using the CD47 agonist peptide 4N1K and blocking monoclonal antibodies (mAbs), we showed that CD47 binds the CBD domain of the endothelial TSP-1 inducing the activation of the platelet IIb 3 integrin which in turn becomes able to link the endothelial receptors ICAM-1 and v 3. Platelet CD36 and GPIb are involved too since, platelet incubation with blocking mAbs directed against each of these two receptors significantly decreased platelet arrest. As anti-CD47 treatment of platelets did not further decrease adhesion of anti-CD36-treated platelets and, as CD36 is a TSP-1 receptor, this suggests that CD36/TSP-1 interaction could trigger the CD47-dependent pathway. Overall, CD47 antagonists would be of significant clinical importance.

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