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.

中文翻译：

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髓过氧化物酶同工型对红细胞生物物理特性的影响。

最近发现，存储在嗜中性粒细胞的嗜酸性颗粒中的一种过氧化物酶，髓过氧化物酶（MPO）会影响红细胞（RBC）的可变形性，从而导致血液微循环异常。天然MPO是一种同型二聚体，由两个相同的protomer（单体MPO）组成，它们通过一个二硫键相连，但由于二硫键裂解而形成的炎症灶中，单体MPO（hemi-MPO）也可以产生。这项研究调查了两种MPO同工型是否对RBC的生物物理特性具有明显的影响。我们发现半-MPO以及二聚体形式与RBC质膜上的糖蛋白A / B和band 3蛋白结合，导致细胞对渗透性和酸性溶血的抵抗力降低，细胞弹性降低，显着变化在细胞体积，形态，和红细胞质膜离子通道的电导 此外，我们首次表明，二聚体和半-MPO均导致RBC膜外叶上的磷脂酰丝氨酸（PS）暴露。然而，与二聚MPO相比，半-MPO对RBC的结构和功能特性的影响要低。这些发现表明，MPO蛋白影响RBC的生物物理特性的能力取决于其构象（二聚体或单体亚型）。令人惊奇的是，推测炎症过程中血液中的半MPO出现可以作为调节机制，以减少由二聚MPO引起的RBC反应异常。我们首次表明，二聚体和半-MPO均可导致RBC膜外小叶上的磷脂酰丝氨酸（PS）暴露。然而，与二聚MPO相比，半-MPO对RBC的结构和功能特性的影响要低。这些发现表明，MPO蛋白影响RBC的生物物理特性的能力取决于其构象（二聚体或单体亚型）。令人惊奇的是，推测炎症过程中血液中的半MPO出现可以作为调节机制，以减少由二聚MPO引起的RBC反应异常。我们首次表明，二聚体和半-MPO均可导致RBC膜外小叶上的磷脂酰丝氨酸（PS）暴露。然而，与二聚MPO相比，半-MPO对RBC的结构和功能特性的影响要低。这些发现表明，MPO蛋白影响RBC的生物物理特性的能力取决于其构象（二聚体或单体亚型）。令人惊奇的是，推测炎症过程中血液中的半MPO出现可以作为调节机制，以减少由二聚MPO引起的RBC反应异常。其生物物理性质取决于其构象（二聚体或单体同工型）。令人惊奇的是，推测炎症过程中血液中的半MPO出现可以作为调节机制，以减少由二聚MPO引起的RBC反应异常。其生物物理性质取决于其构象（二聚体或单体同工型）。令人惊奇的是，推测炎症过程中血液中的半MPO出现可以作为调节机制，以减少由二聚MPO引起的RBC反应异常。