The effect of myeloperoxidase isoforms on biophysical properties of red blood cells
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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.
KeywordsMonomeric myeloperoxidase Dimeric myeloperoxidase Inflammation RBC Phosphatidylserine
This work was partly supported by Russian Foundation for Basic Research (Grant 18-515-00004, Grant 17-54-04009), Belarusian Republican Foundation for Fundamental Research (Grant B18R-058) and Russian President’s grant MD-5133.2018.4.
Compliance with ethical standards
Conflict of interest
The authors declare no competing financial and nonfinancial interests.
This work was approved by the protocol of the Local Ethics Committee at Federal State Budgetary Scientific Institution “Institute of Experimental Medicine”.
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