title: Binding of human myeloperoxidase to red blood cells: Molecular targets and biophysical consequences at the plasma membrane level.
abstract: Myeloperoxidase (MPO) is an oxidant-producing enzyme that can also bind to cellular surface proteins. We found that band 3 protein and glycophorins A and B were the key MPO-binding targets of human red blood cells (RBCs). The interaction of MPO with RBC proteins was mostly electrostatic in nature because it was inhibited by desialation, exogenic sialic acid, high ionic strength, and extreme pH. In addition, MPO failed to interfere with the lectin-induced agglutination of RBCs, suggesting a minor role of glycan-recognizing mechanisms in MPO binding. Multiple biophysical properties of RBCs were altered in the presence of native (i.e., not hypochlorous acid-damaged) MPO. These changes included transmembrane potential, availability of intracellular Ca(2+), and lipid organization in the plasma membrane. MPO-treated erythrocytes became larger in size, structurally more rigid, and hypersensitive to acidic and osmotic hemolysis. Furthermore, we found a significant correlation between the plasma MPO concentration and RBC rigidity index in type-2 diabetes patients with coronary heart disease. These findings suggest that MPO functions as a mediator of novel regulatory mechanism in microcirculation, indicating the influence of MPO-induced abnormalities on RBC deformability under pathological stress conditions.
authors.affiliation: Department of Biophysics, Faculty of Physics, Belarusian State University, Minsk 220030, Belarus.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Gorudko
authors.affiliation: Institute of Experimental Medicine, St. Petersburg, Russia; Saint-Petersburg State University, St. Petersburg, Russia; Research Institute of Physico-Chemical Medicine, Moscow, Russia.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Sokolov
authors.affiliation: Department of Biophysics, Faculty of Physics, Belarusian State University, Minsk 220030, Belarus.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Shamova
authors.affiliation: Department of Biophysics, Faculty of Physics, Belarusian State University, Minsk 220030, Belarus.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Grigorieva
authors.affiliation: Belarusian State Medical University, Minsk, Belarus.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Mironova
authors.affiliation: Institute of Experimental Medicine, St. Petersburg, Russia.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Kudryavtsev
authors.affiliation: Research Institute of Physico-Chemical Medicine, Moscow, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Gusev
authors.affiliation: Research Institute of Physico-Chemical Medicine, Moscow, Russia.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Gusev
authors.affiliation: Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Chekanov
authors.affiliation: Institute of Experimental Medicine, St. Petersburg, Russia; Saint-Petersburg State University, St. Petersburg, Russia.
authors.forename: Vadim B
authors.initials: VB
authors.lastname: Vasilyev
authors.affiliation: Department of Biophysics, Faculty of Physics, Belarusian State University, Minsk 220030, Belarus.
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Cherenkevich
authors.affiliation: Research Institute of Physico-Chemical Medicine, Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia. Electronic address: o-panas@mail.ru.
authors.forename: Oleg M
authors.initials: OM
authors.lastname: Panasenko
authors.affiliation: Department of Biology, Western University, Ontario, London, N6A 5B7, Canada.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Timoshenko
mesh_terms: D001665:Binding Sites; D048429:Cell Size; D002478:Cells, Cultured; D004910:Erythrocyte Membrane / Q000378:metabolism* / Q000648:ultrastructure; D004912:Erythrocytes / Q000166:cytology* / Q000502:physiology*; D006461:Hemolysis / Q000502:physiology*; D006801:Humans; D008560:Membrane Fluidity / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D009195:Peroxidase
keywords: Cardiovascular diseases; Cell deformability; Erythrocytes; Lectin; Myeloperoxidase; Oxidative/halogenative stress