The significance of surface neutrophilic MPO expression level in NETosis and NETosis-associated coagulopathies in covid-19 infected patients

Jamali, Elham; Abbasi, Mojdeh; Tayer, Akbar Hashemi; Monfared, Ali Arabi; Tandel, Parisa; Tamaddon, Gholamhossein; Kazerooni, Ehsan Sarraf; Rakhshandehroo, Shahrokh; Ranjbaran, Reza

doi:10.1016/j.bcmd.2022.102676

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…We observed higher levels of NETosis markers, i.e., MPO and MPO/DNA complexes, in COVID-19 patients overall, which is in line with previous research [8,26,27]. NETosis has been widely associated with the pathophysiology behind severe COVID-19, leading to immunothrombotic events and respiratory failure [3,7].…”

Section: Higher Netosis Markers Are Associated With Complement Activa...supporting

confidence: 91%

The Role of NETosis and Complement Activation in COVID-19-Associated Coagulopathies

et al. 2023

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Inflammation-induced coagulopathy is a common complication associated with coronavirus disease 2019 (COVID-19). We aim to evaluate the association of NETosis and complement markers with each other as well as their association with thrombogenicity and disease severity in COVID-19. The study included hospitalized patients with an acute respiratory infection: patients with SARS-CoV2 infection (COVpos, n = 47) or either pneumonia or infection-triggered acute exacerbated COPD (COVneg, n = 36). Our results show that NETosis, coagulation, and platelets, as well as complement markers, were significantly increased in COVpos patients, especially in severely ill COVpos patients. NETosis marker MPO/DNA complexes correlated with coagulation, platelet, and complement markers only in COVpos. Severely ill COVpos patients showed an association between complement C3 and SOFA (R = 0.48; p ≤ 0.028), C5 and SOFA (R = 0.46; p ≤ 0.038), and C5b-9 and SOFA (R = 0.44; p ≤ 0.046). This study provides further evidence that NETosis and the complement system are key players in COVID-19 inflammation and clinical severity. Unlike previous studies that found NETosis and complement markers to be elevated in COVID-19 patients compared to healthy controls, our findings show that this characteristic distinguishes COVID-19 from other pulmonary infectious diseases. Based on our results, we propose that COVID-19 patients at high risk for immunothrombosis could be identified via elevated complement markers such as C5.

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Section: Higher Netosis Markers Are Associated With Complement Activa...supporting

confidence: 91%

The Role of NETosis and Complement Activation in COVID-19-Associated Coagulopathies

et al. 2023

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“…COVID-19 exploded at the end of 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [216], and seriously disrupted healthcare systems, suppressed economic development, and threatened social stability [217], directly and indirectly. Recent studies have shown a correlation between COVID-19 and MPO, the major particle-resident protein of NETs, as mentioned above [218]. Clinical research on COVID-19 found that levels of MPO were significantly upregulated in the serum of COVID-19 patients compared with healthy individuals, and serum MPO levels in the recovered population were reduced to levels comparable to those in healthy people [21].…”

Section: Lung Diseases and Covid-19mentioning

confidence: 83%

The Roles of Neutrophil-Derived Myeloperoxidase (MPO) in Diseases: The New Progress

Lin,

Chen,

Chen

et al. 2024

Antioxidants

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Myeloperoxidase (MPO) is a heme-containing peroxidase, mainly expressed in neutrophils and, to a lesser extent, in monocytes. MPO is known to have a broad bactericidal ability via catalyzing the reaction of Cl− with H2O2 to produce a strong oxidant, hypochlorous acid (HOCl). However, the overproduction of MPO-derived oxidants has drawn attention to its detrimental role, especially in diseases characterized by acute or chronic inflammation. Broadly speaking, MPO and its derived oxidants are involved in the pathological processes of diseases mainly through the oxidation of biomolecules, which promotes inflammation and oxidative stress. Meanwhile, some researchers found that MPO deficiency or using MPO inhibitors could attenuate inflammation and tissue injuries. Taken together, MPO might be a promising target for both prognostic and therapeutic interventions. Therefore, understanding the role of MPO in the progress of various diseases is of great value. This review provides a comprehensive analysis of the diverse roles of MPO in the progression of several diseases, including cardiovascular diseases (CVDs), neurodegenerative diseases, cancers, renal diseases, and lung diseases (including COVID-19). This information serves as a valuable reference for subsequent mechanistic research and drug development.

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“…NETosis is the result of projections of decondensed chromatin and granular contents, such as MPO, Elastase, and Cit-H3, which effectively immobilize pathogens or cell debris [ 74 ]. However, recent evidence has shown that peripheral NETs can have fewer typical markers, such as MPO, even when Cit-H3 is elevated, mainly because of a change in the surface that can affect the binding of MPO to NETs in the presence of histones [ 78 , 79 ].…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps Release following Hypoxic-Ischemic Brain Injury in Newborn Rats Treated with Therapeutic Hypothermia

Bernis

Zweyer

Maes

et al. 2023

IJMS

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The peripheral immune system plays a critical role in neuroinflammation of the central nervous system after an insult. Hypoxic-ischemic encephalopathy (HIE) induces a strong neuroinflammatory response in neonates, which is often associated with exacerbated outcomes. In adult models of ischemic stroke, neutrophils infiltrate injured brain tissue immediately after an ischemic insult and aggravate inflammation via various mechanisms, including neutrophil extracellular trap (NETs) formation. In this study, we used a neonatal model of experimental hypoxic-ischemic (HI) brain injury and demonstrated that circulating neutrophils were rapidly activated in neonatal blood. We observed an increased infiltration of neutrophils in the brain after exposure to HI. After treatment with either normothermia (NT) or therapeutic hypothermia (TH), we observed a significantly enhanced expression level of the NETosis marker Citrullinated H3 (Cit-H3), which was significantly more pronounced in animals treated with TH than in those treated with NT. NETs and NLR family pyrin domain containing 3 (NLRP-3) inflammasome assembly are closely linked in adult models of ischemic brain injury. In this study, we observed an increase in the activation of the NLRP-3 inflammasome at the time points analyzed, particularly immediately after TH, when we observed a significant increase in NETs structures in the brain. Together, these results suggest the important pathological functions of early arriving neutrophils and NETosis following neonatal HI, particularly after TH treatment, which is a promising starting point for the development of potential new therapeutic targets for neonatal HIE.

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The significance of surface neutrophilic MPO expression level in NETosis and NETosis-associated coagulopathies in covid-19 infected patients

Cited by 5 publications

References 28 publications

The Role of NETosis and Complement Activation in COVID-19-Associated Coagulopathies

The Role of NETosis and Complement Activation in COVID-19-Associated Coagulopathies

The Roles of Neutrophil-Derived Myeloperoxidase (MPO) in Diseases: The New Progress

Neutrophil Extracellular Traps Release following Hypoxic-Ischemic Brain Injury in Newborn Rats Treated with Therapeutic Hypothermia

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