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A peptide from the staphylococcal protein Efb binds P-selectin and inhibits the interaction of platelets with leukocytes

Wallis, Stuart; Wolska, Nina; Englert, Hanna; Posner, Mareike; Upadhyay, Abhishek; Renné, Thomas; Eggleston, Ian; Bagby, Stefan; Pula, Giordano

Authors

Stuart Wallis

Nina Wolska

Hanna Englert

Mareike Posner

Abhishek Upadhyay

Thomas Renné

Ian Eggleston

Stefan Bagby



Abstract

Aims: P-selectin is a key surface adhesion molecule for the interaction of platelets with leukocytes. We have shown previously that the N-terminal domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb) binds to P-selectin and interferes with platelet-leukocyte aggregate formation. Here, we aimed to identify the minimal Efb motif required for binding platelets and to characterize its ability to interfering with the formation of platelet-leukocyte aggregates. Methods and Results: Using a library of synthetic peptides, we mapped the platelet-binding site to a continuous 20 amino acid stretch. The peptide Efb68-87 was able to bind to resting and, to a greater extent, thrombin-stimulated platelets in the absence of fibrinogen. Dot blots, pull-down assays and P-selectin glycoprotein ligand-1 (PSGL-1) competitive binding experiments identified P-selectin as the cellular docking site mediating Efb68-87 platelet binding. Accordingly, Efb68-87 did not bind to other blood cells and captured platelets from human whole blood under low shear stress conditions. Efb68-87 did not affect platelet activation as tested by aggregometry, flow cytometry and immunoblotting, but inhibited the formation of platelet-leukocyte aggregates (PLAs). Efb68-87 also interfered with the platelet-dependent stimulation of neutrophil extracellular traps (NETs) formation in vitro. Conclusions: We have identified Efb68-87 as a novel selective platelet-binding peptide. Efb68-87 binds directly to P-selectin and inhibits interactions of platelets with leukocytes that lead to PLA and NET formation. As PLAs and NETs play a key role in thromboinflammation, Efb68-87 is an exciting candidate for the development of novel selective inhibitors of the proinflammatory activity of platelets.

Citation

Wallis, S., Wolska, N., Englert, H., Posner, M., Upadhyay, A., Renné, T., Eggleston, I., Bagby, S., & Pula, G. (2022). A peptide from the staphylococcal protein Efb binds P-selectin and inhibits the interaction of platelets with leukocytes. Journal of thrombosis and haemostasis : JTH, 20(3), 729-741. https://doi.org/10.1111/jth.15613

Journal Article Type Article
Acceptance Date Nov 29, 2021
Online Publication Date Feb 26, 2022
Publication Date Mar 1, 2022
Deposit Date Jun 4, 2025
Publicly Available Date Jun 19, 2025
Journal Journal of Thrombosis and Haemostasis
Print ISSN 1538-7933
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 20
Issue 3
Pages 729-741
DOI https://doi.org/10.1111/jth.15613
Keywords Leukocyte; Neutrophil extracellular trap; Platelet; Platelet‐leukocyte aggregate; P‐selectin; Thromboinflammation
Public URL https://hull-repository.worktribe.com/output/4619713

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0

Copyright Statement
Copyright © 2021 The Authors. Journal of Thrombosis and Haemostasis published by ELSEVIER INC. on behalf of International Society on Thrombosis and Haemostasis.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.





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