Belarusian State University, Minsk, Belarus.
FSBSI "Institute of Experimental Medicine", St. Petersburg, Russia.
Mol Cell Biochem. 2020 Jan;464(1-2):119-130. doi: 10.1007/s11010-019-03654-0. Epub 2019 Nov 21.
Myeloperoxidase (MPO), an oxidant-producing enzyme, stored in azurophilic granules of neutrophils has been recently shown to influence red blood cell (RBC) deformability leading to abnormalities in blood microcirculation. Native MPO is a homodimer, consisting of two identical protomers (monomeric MPO) connected by a single disulfide bond but in inflammatory foci as a result of disulfide cleavage monomeric MPO (hemi-MPO) can also be produced. This study investigated if two MPO isoforms have distinct effects on biophysical properties of RBCs. We have found that hemi-MPO, as well as the dimeric form, bind to the glycophorins A/B and band 3 protein on RBC's plasma membrane, that lead to reduced cell resistance to osmotic and acidic hemolysis, reduction in cell elasticity, significant changes in cell volume, morphology, and the conductance of RBC plasma membrane ion channels. Furthermore, we have shown for the first time that both dimeric and hemi-MPO lead to phosphatidylserine (PS) exposure on the outer leaflet of RBC membrane. However, the effects of hemi-MPO on the structural and functional properties of RBCs were lower compared to those of dimeric MPO. These findings suggest that the ability of MPO protein to influence RBC's biophysical properties depends on its conformation (dimeric or monomeric isoform). It is intriguing to speculate that hemi-MPO appearance in blood during inflammation can serve as a regulatory mechanism addressed to reduce abnormalities on RBC response, induced by dimeric MPO.
髓过氧化物酶 (MPO) 是一种产氧化剂的酶，储存在中性粒细胞的嗜天青颗粒中，最近研究表明它会影响红细胞 (RBC) 的变形能力，导致血液微循环异常。天然 MPO 是一个由两个相同亚基（单体 MPO）通过一个二硫键连接而成的同源二聚体，但在炎症焦点中，由于二硫键断裂，单体 MPO（半 MPO）也可以产生。本研究探讨了两种 MPO 同工酶是否对 RBC 的生物物理特性有不同的影响。我们发现半 MPO 以及二聚体形式都能与 RBC 质膜上的血型糖蛋白 A/B 和带 3 蛋白结合，导致细胞对渗透压和酸性溶血的抵抗力降低，细胞弹性降低，细胞体积、形态和 RBC 质膜离子通道的电导发生显著变化。此外，我们首次表明，二聚体和半 MPO 都能导致 PS 暴露在 RBC 膜外叶。然而，与二聚体 MPO 相比，半 MPO 对 RBC 结构和功能特性的影响较低。这些发现表明，MPO 蛋白影响 RBC 生物物理特性的能力取决于其构象（二聚体或单体同工酶）。有趣的是，推测在炎症期间血液中出现半 MPO 可以作为一种调节机制，以减轻由二聚体 MPO 诱导的 RBC 反应异常。
