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Annexin A1 mimetic peptide, Ac2-26 induces thromboinflammatory responses in platelets via formyl peptide receptor 2/ALX

Zharkova, O., Salamah, M., Babak, M., Andrade, F., Gil, C., Oliani, S., Lim, L., Vaiyapuri, S. ORCID: https://orcid.org/0000-0002-6006-6517 and Moraes, L. (2020) Annexin A1 mimetic peptide, Ac2-26 induces thromboinflammatory responses in platelets via formyl peptide receptor 2/ALX. Biomedicines. ISSN 2227-9059 (In Press)

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Abstract/Summary

Annexin A1 (ANXA1) is an endogenous protein that plays a central function in the regulation of inflammatory responses. While the role of ANXA1 and its exogenous peptidomimetics, N-Acetyl 2-26 (ANXA1Ac2-26) in the modulation of immunological responses of neutrophils and monocytes has been extensively investigated, their effects on the regulation of platelet reactivity, haemostasis, thrombosis and platelet-mediated inflammatory responses remain largely unexplored. Here, we demonstrate that ANXA1Ac2-26 exerts an activatory role in platelets as characterised by its ability to increase the levels of fibrinogen binding, P-selectin exposure and intracellular calcium mobilisation in platelets. Moreover, ANXA1Ac2-26 increased the formation of platelet-leukocyte aggregates and neutrophil extracellular traps (NETs). The experiments performed using a pharmacological inhibitor (WRW4) for formyl peptide receptor 2/ALX (FPR2/ALX), and platelets obtained from Fpr2/3 (orthologue of human FPR2/ALX)-deficient mice revealed that the effects of ANXA1Ac2-26 are largely mediated through FPR2/ALX in platelets. Moreover, the deletion of Anxa1 in mice resulted in increased platelet reactivity for ANXA1Ac2-26 and this can be attributed to the elevated level of Fpr2/3 in these mice platelets. Together, this study demonstrates that in addition to its ability to modulate inflammatory responses via leukocytes, ANXA1Ac2-26 can activate platelets in order to modulate haemostasis, thrombosis and platelet-mediated inflammatory responses under various pathophysiological settings.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:95195
Publisher:MDPI

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