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The formyl peptide fMLF primes platelet activation and augments thrombus formation
Author(s) -
Salamah Maryam F.,
Ravishankar Divyashree,
Vaiyapuri Rajendran,
Moraes Leonardo A.,
Patel Ketan,
Perretti Mauro,
Gibbins Jonathan M.,
Vaiyapuri Sakthivel
Publication year - 2019
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14466
Subject(s) - platelet activation , platelet , n formylmethionine leucyl phenylalanine , innate immune system , chemotaxis , formyl peptide receptor , hemostasis , receptor , immunology , microbiology and biotechnology , chemistry , immune system , biology , biochemistry , medicine
Essentials The role of formyl peptide receptor 1 (FPR1) and its ligand, fMLF, in the regulation of platelet function, hemostasis, and thrombosis is largely unknown. Fpr1 ‐deficient mice and selective inhibitors for FPR1 were used to investigate the function of fMLF and FPR1 in platelets. N‐formyl‐methionyl‐leucyl‐phenylalanine primes platelet activation and augments thrombus formation, mainly through FPR1 in platelets. Formyl peptide receptor 1 plays a pivotal role in the regulation of platelet function.Background Formyl peptide receptors (FPRs) play pivotal roles in the regulation of innate immunity and host defense. The FPRs include three family members: FPR1, FPR2/ALX, and FPR3. The activation of FPR1 by its high‐affinity ligand, N ‐formyl‐methionyl‐leucyl‐phenylalanine (fMLF) (a bacterial chemoattractant peptide), triggers intracellular signaling in immune cells such as neutrophils and exacerbates inflammatory responses to accelerate the clearance of microbial infection. Notably, fMLF has been demonstrated to induce intracellular calcium mobilization and chemotaxis in platelets that are known to play significant roles in the regulation of innate immunity and inflammatory responses. Despite a plethora of research focused on the roles of FPR1 and its ligands such as fMLF on the modulation of immune responses, their impact on the regulation of hemostasis and thrombosis remains unexplored. Objective To determine the effects of fMLF on the modulation of platelet reactivity, hemostasis, and thrombus formation. Methods Selective inhibitors for FPR1 and Fpr1 ‐deficient mice were used to determine the effects of fMLF and FPR1 on platelets using various platelet functional assays. Results N ‐formyl‐methionyl‐leucyl‐phenylalanine primes platelet activation through inducing distinctive functions and enhances thrombus formation under arterial flow conditions. Moreover, FPR1 regulates normal platelet function as its deficiency in mouse or blockade in human platelets using a pharmacological inhibitor resulted in diminished agonist‐induced platelet activation. Conclusion Since FPR1 plays critical roles in numerous disease conditions, its influence on the modulation of platelet activation and thrombus formation may provide insights into the mechanisms that control platelet‐mediated complications under diverse pathological settings.