Background: Formyl peptide receptor 2/ALX (FPR2/ALX), a member of seven transmembrane G protein-coupled receptors superfamily, exhibits dual effects of pro- and anti-inflammatory responses based on the nature of stimulating ligand type. Recently, FPRs have been shown to be present in platelets. However, FPR2/ALX and the effect of its anti-inflammatory ligands on the regulation of platelet function has not been addressed yet. Platelets play significant roles in the regulation of inflammation and host defence in addition to haemostasis and thrombosis. They act as sentinels through regulating inflammatory responses due to their large number in circulation and their ability to rapidly release different kinds of immunomodulatory cytokines, and other inflammatory mediators.

Aims: Given the anti-inflammatory effects of FPR2/ALX ligands, we sought to study the role of its anti-inflammatory ligand, Lipoxin A4 analogue, BML-111 in regulating platelet activation and thrombus formation.

Methods: The expression of FPR2/ALX in human and murine platelets as well as megakaryocytes was confirmed using immunoblot analysis. The subcellular distribution of FPR2/ALX in platelets was demonstrated by immunofluorescence.

Results: BML-111 inhibited a range of platelet function such as aggregation, fibrinogen binding to integrin α_IIbβ₃, 𝛼 -granule secretion, dense granule secretion, platelet spreading, and clot retraction suggesting that it may act as a modulator of platelet function.

Conclusions: This study demonstrates the significance of FPR2/ALX and its anti-inflammatory ligand, BML-111 in the modulation of platelet function. This suggests that FPR2/ALX may act as novel target to control thrombo-inflammatory conditions.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/role-of-formyl-peptide-receptor-2-fpr2-alx-and-its-anti-inflammatory-ligand-lipoxin-a4-analogue-bml-111-in-the-modulation-of-platelet-function/