Deletion of annexin A1 in mice upregulates the expression of its receptor, Fpr2/3, and reactivity to the AnxA1 mimetic peptide in platelets

Zharkova, O., Salamah, M. F., Babak, M. V., Rajan, E., Lim, L. H. K., Andrade, F., Gil, C. D., Oliani, S. M., Moraes, L. and Vaiyapuri, S. ORCID: https://orcid.org/0000-0002-6006-6517 (2023) Deletion of annexin A1 in mice upregulates the expression of its receptor, Fpr2/3, and reactivity to the AnxA1 mimetic peptide in platelets. International Journal of Molecular Sciences, 24 (4). 3424. ISSN 1422-0067 doi: 10.3390/ijms24043424

Abstract/Summary

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 (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 recep-tor 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 exposure of P-selectin on the surface. Moreover, ANXA1Ac2-26 increased the development of platelet-leukocyte aggregates in whole blood. The experiments carried out us-ing 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 inflamma-tory responses via leukocytes, ANXA1 modulates platelet function which may influence throm-bosis, haemostasis, and platelet-mediated inflammation under various pathophysiological settings.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/110520
Identification Number/DOI	10.3390/ijms24043424
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Publisher	MDPI
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