Deletion of Annexin A1 in Mice Upregulates the Expression of Its Receptor, Fpr2/3, and Reactivity to the AnxA1 Mimetic Peptide in Platelets

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Olga Zharkova
  • Maryam F. Salamah
  • Elanchezhian Rajan
  • Lina H. K. Lim
  • Frans Andrade
  • Cristiane D. Gil
  • Sonia M. Oliani
  • Leonardo A. Moraes
  • Sakthivel Vaiyapuri

Related Research Unit(s)

Detail(s)

Original languageEnglish
Article number3424
Journal / PublicationInternational Journal of Molecular Sciences
Volume24
Issue number4
Online published8 Feb 2023
Publication statusPublished - Feb 2023

Link(s)

Abstract

Annexin A1 (ANXA1) is an endogenous protein, which plays a central function in the modulation of inflammation. While the functions of ANXA1 and its exogenous peptidomimetics, N-Acetyl 2-26 ANXA1-derived peptide (ANXA1Ac2-26), in the modulation of immunological responses of neutrophils and monocytes have been investigated in detail, their effects on the modulation of platelet reactivity, haemostasis, thrombosis, and platelet-mediated inflammation remain largely unknown. Here, we demonstrate that the deletion of Anxa1 in mice upregulates the expression of its receptor, formyl peptide receptor 2/3 (Fpr2/3, orthologue of human FPR2/ALX). As a result, the addition of ANXA1Ac2-26 to platelets exerts an activatory role in platelets, as characterised by its ability to increase the levels of fibrinogen binding and the exposure of P-selectin on the surface. Moreover, ANXA1Ac2-26 increased the development of platelet-leukocyte aggregates in whole blood. The experiments carried out using a pharmacological inhibitor (WRW4) for FPR2/ALX, and platelets isolated from Fpr2/3-deficient mice ascertained that the actions of ANXA1Ac2-26 are largely mediated through Fpr2/3 in platelets. Together, this study demonstrates that in addition to its ability to modulate inflammatory responses via leukocytes, ANXA1 modulates platelet function, which may influence thrombosis, haemostasis, and platelet-mediated inflammation under various pathophysiological settings. © 2023 by the authors.

Research Area(s)

  • annexin A1, ANXA1Ac2-26, FPR2/ALX, inflammation, thromboinflammation, thrombosis

Citation Format(s)

Deletion of Annexin A1 in Mice Upregulates the Expression of Its Receptor, Fpr2/3, and Reactivity to the AnxA1 Mimetic Peptide in Platelets. / Zharkova, Olga; Salamah, Maryam F.; Babak, Maria V. et al.
In: International Journal of Molecular Sciences, Vol. 24, No. 4, 3424, 02.2023.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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