• Je něco špatně v tomto záznamu ?

Red blood cells serve as intravascular carriers of myeloperoxidase

M. Adam, S. Gajdova, H. Kolarova, L. Kubala, D. Lau, A. Geisler, T. Ravekes, V. Rudolph, PS. Tsao, S. Blankenberg, S. Baldus, A. Klinke,

. 2014 ; 74 (-) : 353-63.

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc15014183

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc15014183
003      
CZ-PrNML
005      
20150428101401.0
007      
ta
008      
150420s2014 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.yjmcc.2014.06.009 $2 doi
035    __
$a (PubMed)24976018
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Adam, Matti $u Stanford University, Division of Cardiovascular Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford, CA, USA. Electronic address: matti.adam@stanford.edu. $7 gn_A_00001111
245    10
$a Red blood cells serve as intravascular carriers of myeloperoxidase / $c M. Adam, S. Gajdova, H. Kolarova, L. Kubala, D. Lau, A. Geisler, T. Ravekes, V. Rudolph, PS. Tsao, S. Blankenberg, S. Baldus, A. Klinke,
520    9_
$a 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.
650    _2
$a akutní koronární syndrom $x krev $x patologie $7 D054058
650    _2
$a zvířata $7 D000818
650    _2
$a aorta $x účinky léků $7 D001011
650    _2
$a biologický transport $7 D001692
650    _2
$a kultivované buňky $7 D002478
650    _2
$a cévní endotel $x účinky léků $7 D004730
650    _2
$a erytrocyty $x metabolismus $x patologie $7 D004912
650    _2
$a srdce $x účinky léků $7 D006321
650    _2
$a srdeční selhání $x krev $x patologie $7 D006333
650    _2
$a heparin $x chemie $7 D006493
650    _2
$a lidé $7 D006801
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a myši $7 D051379
650    _2
$a myši inbrední C57BL $7 D008810
650    _2
$a oxid dusnatý $x metabolismus $x farmakologie $7 D009569
650    _2
$a orgánové kultury - kultivační techniky $7 D009924
650    _2
$a peroxidasa $x krev $x farmakologie $7 D009195
650    _2
$a vazba proteinů $7 D011485
650    _2
$a techniky tkáňových kultur $7 D046509
650    _2
$a cévní rezistence $x účinky léků $7 D014655
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Gajdova, Silvie $u Academy of Sciences of the Czech Republic, Institute of Biophysics, Brno, Czech Republic.
700    1_
$a Kolarova, Hana $u Academy of Sciences of the Czech Republic, Institute of Biophysics, Brno, Czech Republic.
700    1_
$a Kubala, Lukas $u Academy of Sciences of the Czech Republic, Institute of Biophysics, Brno, Czech Republic; International Clinical Research Center-CBCE, St. Anne's University Hospital Brno, Brno, Czech Republic.
700    1_
$a Lau, Denise $u University of Hamburg, Heart Center, Department of Cardiovascular Medicine, Hamburg, Germany.
700    1_
$a Geisler, Anne $u University of Hamburg, Heart Center, Department of Cardiovascular Medicine, Hamburg, Germany.
700    1_
$a Ravekes, Thorben $u Heart Center, Department of Cardiology and Cologne Cardiovascular Research Center, University of Cologne, Cologne, Germany.
700    1_
$a Rudolph, Volker $u Heart Center, Department of Cardiology and Cologne Cardiovascular Research Center, University of Cologne, Cologne, Germany.
700    1_
$a Tsao, Philip S $u Stanford University, Division of Cardiovascular Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford, CA, USA.
700    1_
$a Blankenberg, Stefan $u University of Hamburg, Heart Center, Department of Cardiovascular Medicine, Hamburg, Germany.
700    1_
$a Baldus, Stephan $u Heart Center, Department of Cardiology and Cologne Cardiovascular Research Center, University of Cologne, Cologne, Germany.
700    1_
$a Klinke, Anna $u Heart Center, Department of Cardiology and Cologne Cardiovascular Research Center, University of Cologne, Cologne, Germany.
773    0_
$w MED00002807 $t Journal of molecular and cellular cardiology $x 1095-8584 $g Roč. 74, č. - (2014), s. 353-63
856    41
$u https://pubmed.ncbi.nlm.nih.gov/24976018 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20150420 $b ABA008
991    __
$a 20150428101704 $b ABA008
999    __
$a ok $b bmc $g 1071764 $s 897061
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2014 $b 74 $c - $d 353-63 $i 1095-8584 $m Journal of Molecular and Cellular Cardiology $n J Mol Cell Cardiol $x MED00002807
LZP    __
$a Pubmed-20150420

Najít záznam

Citační ukazatele

Možnosti archivace