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Involvement of a CD47-dependent pathway in platelet adhesion on inflamed vascular endothelium under flow.
Blood. 2003 Jun 15; 101(12):4836-43.Blood

Abstract

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, though 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 tumor necrosis factor-alpha (TNF-alpha)-stimulated vascular endothelial cells. Using the CD47 agonist peptide 4N1K and blocking monoclonal antibodies (mAbs), we showed that CD47 binds the cell-binding domain (CBD) of endothelial thrombospondin-1 (TSP-1), inducing activation of the platelet alphaIIbbeta3 integrin that in turn becomes able to link the endothelial receptors intercellular adhesion molecule 1 (ICAM-1) and alphavbeta3. Platelet CD36 and GPIbalpha are also involved because platelet incubation with blocking mAbs directed against each of these 2 receptors significantly decreased platelet arrest. Given that anti-CD47 treatment of platelets did not further decrease the adhesion of anti-CD36-treated platelets and CD36 is a TSP-1 receptor, it appears that CD36/TSP-1 interaction could trigger the CD47-dependent pathway. Overall, CD47 antagonists may be potentially useful to inhibit platelet adhesion on inflamed endothelium.

Authors+Show Affiliations

Unité Institut National de la Santé et de la Recherche Médicale (INSERM) U343 et Laboratoire d'Immunologie, Nice, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12609828

Citation

Lagadec, Patricia, et al. "Involvement of a CD47-dependent Pathway in Platelet Adhesion On Inflamed Vascular Endothelium Under Flow." Blood, vol. 101, no. 12, 2003, pp. 4836-43.
Lagadec P, Dejoux O, Ticchioni M, et al. Involvement of a CD47-dependent pathway in platelet adhesion on inflamed vascular endothelium under flow. Blood. 2003;101(12):4836-43.
Lagadec, P., Dejoux, O., Ticchioni, M., Cottrez, F., Johansen, M., Brown, E. J., & Bernard, A. (2003). Involvement of a CD47-dependent pathway in platelet adhesion on inflamed vascular endothelium under flow. Blood, 101(12), 4836-43.
Lagadec P, et al. Involvement of a CD47-dependent Pathway in Platelet Adhesion On Inflamed Vascular Endothelium Under Flow. Blood. 2003 Jun 15;101(12):4836-43. PubMed PMID: 12609828.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of a CD47-dependent pathway in platelet adhesion on inflamed vascular endothelium under flow. AU - Lagadec,Patricia, AU - Dejoux,Olivier, AU - Ticchioni,Michel, AU - Cottrez,Françoise, AU - Johansen,Mette, AU - Brown,Eric J, AU - Bernard,Alain, Y1 - 2003/02/27/ PY - 2003/3/1/pubmed PY - 2004/2/5/medline PY - 2003/3/1/entrez SP - 4836 EP - 43 JF - Blood JO - Blood VL - 101 IS - 12 N2 - 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, though 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 tumor necrosis factor-alpha (TNF-alpha)-stimulated vascular endothelial cells. Using the CD47 agonist peptide 4N1K and blocking monoclonal antibodies (mAbs), we showed that CD47 binds the cell-binding domain (CBD) of endothelial thrombospondin-1 (TSP-1), inducing activation of the platelet alphaIIbbeta3 integrin that in turn becomes able to link the endothelial receptors intercellular adhesion molecule 1 (ICAM-1) and alphavbeta3. Platelet CD36 and GPIbalpha are also involved because platelet incubation with blocking mAbs directed against each of these 2 receptors significantly decreased platelet arrest. Given that anti-CD47 treatment of platelets did not further decrease the adhesion of anti-CD36-treated platelets and CD36 is a TSP-1 receptor, it appears that CD36/TSP-1 interaction could trigger the CD47-dependent pathway. Overall, CD47 antagonists may be potentially useful to inhibit platelet adhesion on inflamed endothelium. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/12609828/Involvement_of_a_CD47_dependent_pathway_in_platelet_adhesion_on_inflamed_vascular_endothelium_under_flow_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)50647-2 DB - PRIME DP - Unbound Medicine ER -