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Updated: Feb 12, 2026
Quantifying Myeloperoxidase-DNA and Neutrophil Elastase-DNA Complexes from Neutrophil Extracellular Traps by Using a Modified Sandwich ELISA
Published on: May 12, 2023
Neutrophil activation in response to monomeric myeloperoxidase
Irina V Gorudko1, Daria V Grigorieva1, Alexey V Sokolov2,3,4,5
1a Belarusian State University, Minsk 220030, Belarus.
Abstract:
Myeloperoxidase (MPO) is an oxidant-producing enzyme that can also regulate cellular functions via its nonenzymatic effects. Mature active MPO isolated from normal human neutrophils is a 145 kDa homodimer, which consists of 2 identical protomers, connected by a single disulfide bond. By binding to CD11b/CD18 integrin, dimeric MPO induces neutrophil activation and adhesion augmenting leukocyte accumulation at sites of inflammation. This study was performed to compare the potency of dimeric and monomeric MPO to elicit selected neutrophil responses. Monomeric MPO (hemi-MPO) was obtained by treating the dimeric MPO by reductive alkylation. Analysis of the crucial signal transducer, intracellular Ca2+, showed that dimeric MPO induces Ca2+ mobilization from the intracellular calcium stores of neutrophils and influx of extracellular Ca2+ whereas the effect of monomeric MPO on Ca2+ increase in neutrophils was less. It was also shown that monomeric MPO was less efficient than dimeric MPO at inducing actin cytoskeleton reorganization, cell survival, and neutrophil degranulation. Furthermore, we have detected monomeric MPO in the blood plasma of patients with acute inflammation. Our data suggest that the decomposition of dimeric MPO into monomers can serve as a regulatory mechanism that controls MPO-dependent activation of neutrophils and reduces the proinflammatory effects of MPO.
Insights
Dimeric myeloperoxidase (MPO) strongly activates neutrophils, but its monomeric form is less potent. This suggests MPO
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Myeloperoxidase (MPO) is an enzyme produced by neutrophils, known for its role in producing oxidants.
- MPO also influences cellular functions through nonenzymatic mechanisms.
- Dimeric MPO binds to CD11b/CD18 integrin, promoting neutrophil activation and adhesion, which contributes to inflammation.
Purpose of the Study:
- To compare the efficacy of dimeric and monomeric MPO in eliciting neutrophil responses.
- To investigate the role of MPO's structural form in neutrophil activation and inflammatory processes.
Main Methods:
- Monomeric MPO (hemi-MPO) was generated from dimeric MPO via reductive alkylation.
- Neutrophil responses including intracellular calcium (Ca2+) mobilization, actin cytoskeleton reorganization, cell survival, and degranulation were analyzed.
- MPO forms were detected in the blood plasma of patients with acute inflammation.
Main Results:
- Dimeric MPO effectively induced intracellular Ca2+ mobilization and extracellular Ca2+ influx in neutrophils.
- Monomeric MPO demonstrated significantly reduced potency in increasing intracellular Ca2+ levels compared to dimeric MPO.
- Monomeric MPO was less efficient than dimeric MPO in promoting actin cytoskeleton reorganization, cell survival, and neutrophil degranulation.
Conclusions:
- The decomposition of dimeric MPO into monomers may act as a regulatory mechanism controlling neutrophil activation.
- This structural transition of MPO can modulate its pro-inflammatory effects.
- Monomeric MPO was identified in the plasma of patients experiencing acute inflammation, supporting its in vivo relevance.
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