title: Myeloperoxidase induces the priming of platelets.
abstract: The release of myeloperoxidase (MPO) from polymorphonuclear neutrophils is a hallmark of vascular inflammation and contributes to the pathogenesis of vascular inflammatory processes. However, the effects of MPO on platelets as a contributory mechanism in vascular inflammatory diseases remain unknown. Thus, MPO interaction with platelets and its effects on platelet function were examined. First, dose-dependent binding of MPO (between 1.7 and 13.8nM) to both human and mouse platelets was observed. This was in direct contrast to the absence of MPO in megakaryocytes. MPO was localized both on the surface of and inside platelets. Cytoskeleton inhibition did not prevent MPO localization inside the three-dimensional platelet structure. MPO peroxidase activity was preserved upon the MPO binding to platelets. MPO sequestered in platelets catabolized NO, documented by the decreased production of NO (on average, an approximately 2-fold decrease). MPO treatment did not affect the viability of platelets during short incubations; however, it decreased platelet viability after long-term storage for 7 days (an approximately 2-fold decrease). The activation of platelets by MPO was documented by an MPO-mediated increase in the expression of surface platelet receptors P-selectin and PECAM-1 (of about 5 to 20%) and the increased formation of reactive oxygen species (of about 15 to 200%). However, the activation was only partial, as MPO did not induce the aggregation of platelets nor potentiate platelet response to classical activators. Nor did MPO induce a significant release of the content of granules. The activation of platelets by MPO was connected with increased MPO-treated platelet interaction with polymorphonuclear leukocytes (an approximately 1.2-fold increase) in vitro. In conclusion, it can be suggested that MPO can interact with and activate platelets, which can induce priming of platelets, rather than the classical robust activation of platelets. This can contribute to the development of chronic inflammatory processes in vessels.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic; Department of Animal Physiology, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors.forename: H
authors.initials: H
authors.lastname: Kolarova
authors.affiliation: Department of Cardiology, University Heart Center Hamburg, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Klinke
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic; Department of Animal Physiology, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors.forename: S
authors.initials: S
authors.lastname: Kremserova
authors.affiliation: Department of Cardiology, University Heart Center Hamburg, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Adam
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Pekarova
authors.affiliation: Department of Cardiology, University Heart Center Hamburg, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Baldus
authors.affiliation: Division of Pulmonary/Critical Care Medicine, Department of Internal Medicine, School of Medicine, University of California at Davis, Davis, CA, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Eiserich
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic; International Clinical Research Center-Center of Biomolecular and Cellular Engineering, St. Anne's University Hospital Brno, Brno, Czech Republic. Electronic address: kubalal@ibp.cz.
authors.forename: L
authors.initials: L
authors.lastname: Kubala
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology; D009195:Peroxidase / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects
chemical_list: D009569:Nitric Oxide; D009195:Peroxidase
keywords: Adhesion; Cardiovascular diseases; Free radicals; Hemostasis; Inflammation; Myeloperoxidase; Nitric oxide; Platelets