title: Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry.
abstract: Myeloperoxidase (MPO) is a heme-containing enzyme released from activated leukocytes into the extracellular space during inflammation. Its main function is the production of hypohalous acids that are potent oxidants. MPO can also modulate cell signaling and inflammatory responses independently of its enzymatic activity. Because MPO is regarded as an important risk factor for cardiovascular diseases associated with increased platelet activity, we studied the effects of MPO on human platelet functional properties. Laser scanning confocal microscopy was used to reveal carbohydrate-independent MPO binding to human platelet membrane. Adding MPO to platelets did not activate their aggregation under basal conditions (without agonist). In contrast, MPO augmented agonist-induced platelet aggregation, which was not prevented by MPO enzymatic activity inhibitors. It was found that exposure of platelets to MPO leads to actin cytoskeleton reorganization and an increase in their elasticity. Furthermore, MPO evoked a rise in cytosolic Ca(2+) through enhancement of store-operated Ca(2+) entry (SOCE). Together, these findings indicate that MPO is not a direct agonist but rather a mediator that binds to human platelets, induces actin cytoskeleton reorganization and affects the mechanical stiffness of human platelets, resulting in potentiating SOCE and agonist-induced human platelet aggregation. Therefore, an increased activity of platelets in vascular disease can, at least partly, be provided by MPO elevated concentrations.
authors.affiliation: Department of Biophysics, Belarusian State University , 220030 Minsk, Belarus.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Gorudko
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Sokolov
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Shamova
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Grudinina
authors.forename: Elizaveta S
authors.initials: ES
authors.lastname: Drozd
authors.forename: Ludmila M
authors.initials: LM
authors.lastname: Shishlo
authors.forename: Daria V
authors.initials: DV
authors.lastname: Grigorieva
authors.forename: Sergey B
authors.initials: SB
authors.lastname: Bushuk
authors.forename: Boris A
authors.initials: BA
authors.lastname: Bushuk
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Chizhik
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Cherenkevich
authors.forename: Vadim B
authors.initials: VB
authors.lastname: Vasilyev
authors.forename: Oleg M
authors.initials: OM
authors.lastname: Panasenko
keywords: Actin cytoskeleton; Aggregation; Myeloperoxidase; Platelets; SOCE