Universität zu Köln

Adam, Matti ORCID: 0000-0002-6990-8135, Gajdova, Silvie, Kolarova, Hana, Kubala, Lukas ORCID: 0000-0002-7729-7338, Lau, Denise, Geisler, Anne, Ravekes, Thorben, Rudolph, Volker, Tsao, Philip S., Blankenberg, Stefan, Baldus, Stephan and Klinke, Anna (2014). Red blood cells serve as intravascular carriers of myeloperoxidase. J. Mol. Cell. Cardiol., 74. S. 353 - 364. OXFORD: ELSEVIER SCI LTD. ISSN 1095-8584

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Abstract

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. (C) 2014 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Adam, Matti UNSPECIFIED orcid.org/0000-0002-6990-8135 UNSPECIFIED Gajdova, Silvie UNSPECIFIED UNSPECIFIED UNSPECIFIED Kolarova, Hana UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubala, Lukas UNSPECIFIED orcid.org/0000-0002-7729-7338 UNSPECIFIED Lau, Denise UNSPECIFIED UNSPECIFIED UNSPECIFIED Geisler, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Ravekes, Thorben UNSPECIFIED UNSPECIFIED UNSPECIFIED Rudolph, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsao, Philip S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Blankenberg, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Baldus, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Klinke, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-430962
DOI:	10.1016/j.yjmcc.2014.06.009
Journal or Publication Title:	J. Mol. Cell. Cardiol.
Volume:	74
Page Range:	S. 353 - 364
Date:	2014
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1095-8584
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MICROBICIDAL ACTIVITY; NATRIURETIC-PEPTIDE; HEART-FAILURE; ACTIVATION; INJURY; RISK; INFLAMMATION; NEUTROPHILS; MECHANISMS; IMPACT Multiple languages Cardiac & Cardiovascular Systems; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43096