Abstract Number: PB1840
Meeting: ISTH 2020 Congress
Background: Platelets and neutrophils interact during an infection, inflammation and thrombosis and regulate functions of each other. These interactions are mostly initiated by soluble mediators. One of the principal enzymes of neutrophils is myeloperoxidase (MPO). It is a heme protein that not only generates cytotoxic oxidants but also modulates cellular signal cascades. Hypochlorous acid (HOCl) produced by MPO is the main bactericidal agent that can also damage host biomolecules, and MPO can be one of the primary targets.
Aims: To investigate the ability of HOCl-modified MPO (MPO-HOCl) to affect platelet´s and neutrophil´s functional responses.
Methods: Purified MPO was pre-treated with HOCl at room temperature for 2 h before analysis. The Western blotting, fluorescence and surface-enhanced Raman scattering techniques were used to analyze MPO structure after treatment with HOCl. Cell activation was investigated via aggregometry, flow cytometry, fluorescence techniques.
Results: Flow cytometry analysis and confocal microscopy revealed efficient binding of MPO (25-200 nМ) to human neutrophils and platelets while HOCl-modified MPO displayed significantly reduced binding to cellular surface. Though MPO-HOCl induced calcium signaling in neutrophils, this effect was less than the effect of native MPO and decreased with increasing protein modification by HOCl. However, MPO-HOCl failed to induce exocytosis of lactoferrin, marker of specific granule, and elastase, marker of azurophilic granule in neutrophils. MPO-HOCl in contrast to native MPO did not enhance ADP- and thrombin-induced platelet aggregation and wasn’t able to induce formation of platelet-leukocyte aggregates.
Conclusions: Elevated level of MPO in circulation is associated with inflammation and increased oxidative stress. Our data suggests that MPO can have dual effect:
(i) regulating of platelet and neutrophil activity in order to induce pro-inflammatory responses
(ii) under oxidative stress HOCl-induced modification of MPO down-regulates chronic inflammatory processes in vessels.
This work was partly supported by grant MD-1901.2020.4.
To cite this abstract in AMA style:Gorudko I, Grigorieva D, Shamova E, Kohan A, Panasenko O, Sokolov A. Influence of HOCl-modified Myeloperoxidase on Platelet and Neutrophil Activity [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/influence-of-hocl-modified-myeloperoxidase-on-platelet-and-neutrophil-activity/. Accessed May 6, 2021.
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