Myeloperoxidase induces the priming of platelets

H. Kolarova, A. Klinke, S. Kremserova, M. Adam, M. Pekarova, S. Baldus, J. P. Eiserich, L. Kubala

Research output: Contribution to journalArticle

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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 13.8 nM) 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.

Original languageEnglish (US)
Pages (from-to)357-369
Number of pages13
JournalFree Radical Biology and Medicine
Volume61
DOIs
StatePublished - 2013

Fingerprint

Platelets
Peroxidase
Blood Platelets
Platelet Activation
Chemical activation
Blood Vessels
Neutrophils
CD31 Antigens
P-Selectin
Megakaryocytes
Cytoskeleton
Vascular Diseases
Platelet Aggregation

Keywords

  • Adhesion
  • Cardiovascular diseases
  • Free radicals
  • Hemostasis
  • Inflammation
  • Myeloperoxidase
  • Nitric oxide
  • Platelets

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Kolarova, H., Klinke, A., Kremserova, S., Adam, M., Pekarova, M., Baldus, S., ... Kubala, L. (2013). Myeloperoxidase induces the priming of platelets. Free Radical Biology and Medicine, 61, 357-369. https://doi.org/10.1016/j.freeradbiomed.2013.04.014

Myeloperoxidase induces the priming of platelets. / Kolarova, H.; Klinke, A.; Kremserova, S.; Adam, M.; Pekarova, M.; Baldus, S.; Eiserich, J. P.; Kubala, L.

In: Free Radical Biology and Medicine, Vol. 61, 2013, p. 357-369.

Research output: Contribution to journalArticle

Kolarova, H, Klinke, A, Kremserova, S, Adam, M, Pekarova, M, Baldus, S, Eiserich, JP & Kubala, L 2013, 'Myeloperoxidase induces the priming of platelets', Free Radical Biology and Medicine, vol. 61, pp. 357-369. https://doi.org/10.1016/j.freeradbiomed.2013.04.014
Kolarova H, Klinke A, Kremserova S, Adam M, Pekarova M, Baldus S et al. Myeloperoxidase induces the priming of platelets. Free Radical Biology and Medicine. 2013;61:357-369. https://doi.org/10.1016/j.freeradbiomed.2013.04.014
Kolarova, H. ; Klinke, A. ; Kremserova, S. ; Adam, M. ; Pekarova, M. ; Baldus, S. ; Eiserich, J. P. ; Kubala, L. / Myeloperoxidase induces the priming of platelets. In: Free Radical Biology and Medicine. 2013 ; Vol. 61. pp. 357-369.
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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 13.8 nM) 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.",
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