Red blood cells serve as intravascular carriers of myeloperoxidase
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24976018
DOI
10.1016/j.yjmcc.2014.06.009
PII: S0022-2828(14)00203-X
Knihovny.cz E-resources
- Keywords
- Cell membranes, Erythrocyte, Myeloperoxidase, Systemic vascular resistance, Vascular endothelium-dependent relaxation,
- MeSH
- Acute Coronary Syndrome blood pathology MeSH
- Aorta drug effects MeSH
- Biological Transport MeSH
- Endothelium, Vascular drug effects MeSH
- Vascular Resistance drug effects MeSH
- Erythrocytes metabolism pathology MeSH
- Heparin chemistry MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Organ Culture Techniques MeSH
- Nitric Oxide metabolism pharmacology MeSH
- Peroxidase blood pharmacology MeSH
- Heart drug effects MeSH
- Heart Failure blood pathology MeSH
- Tissue Culture Techniques MeSH
- Protein Binding MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Heparin MeSH
- Nitric Oxide MeSH
- Peroxidase MeSH
Myeloperoxidase (MPO) is a heme enzyme abundantly expressed in polymorphonuclear neutrophils. MPO is enzymatically capable of catalyzing the generation of reactive oxygen species (ROS) and the consumption of nitric oxide (NO). Thus MPO has both potent microbicidal and, upon binding to the vessel wall, pro-inflammatory properties. Interestingly, MPO - a highly cationic protein - has been shown to bind to both endothelial cells and leukocyte membranes. Given the anionic surface charge of red blood cells, we investigated binding of MPO to erythrocytes. Red blood cells (RBCs) derived from patients with elevated MPO plasma levels showed significantly higher amounts of MPO by flow cytometry and ELISA than healthy controls. Heparin-induced MPO-release from patient-derived RBCs was significantly increased compared to controls. Ex vivo experiments revealed dose and time dependency for MPO-RBC binding, and immunofluorescence staining as well as confocal microscopy localized MPO-RBC interaction to the erythrocyte plasma membrane. NO-consumption by RBC-membrane fragments (erythrocyte "ghosts") increased with incrementally greater concentrations of MPO during incubation, indicating preserved catalytic MPO activity. In vivo infusion of MPO-loaded RBCs into C57BL/6J mice increased local MPO tissue concentrations in liver, spleen, lung, and heart tissue as well as within the cardiac vasculature. Further, NO-dependent relaxation of aortic rings was altered by RBC bound-MPO and systemic vascular resistance significantly increased after infusion of MPO-loaded RBCs into mice. In summary, we find that MPO binds to RBC membranes in vitro and in vivo, is transported by RBCs to remote sites in mice, and affects endothelial function as well as systemic vascular resistance. RBCs may avidly bind circulating MPO, and act as carriers of this leukocyte-derived enzyme.
Academy of Sciences of the Czech Republic Institute of Biophysics Brno Czech Republic
University of Hamburg Heart Center Department of Cardiovascular Medicine Hamburg Germany
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