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Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients

Neutrophil Extracellular Traps (NETs) are a contributing factor of vascular thrombosis and alveolar damage in COVID-19 patients. As enoxaparin is currently used to inhibit vascular thrombosis, this study aimed to investigate whether enoxaparin also reduced inflammation and NETs in COVID-19 patients....

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Autores principales: Saithong, Supichcha, Saisorn, Wilasinee, Tovichayathamrong, Punyot, Filbertine, Grace, Torvorapanit, Pattama, Wright, Helen L., Edwards, Steven W., Leelahavanichkul, Asada, Hirankarn, Nattiya, Chiewchengchol, Direkrit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102387/
https://www.ncbi.nlm.nih.gov/pubmed/35563204
http://dx.doi.org/10.3390/ijms23094805
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author Saithong, Supichcha
Saisorn, Wilasinee
Tovichayathamrong, Punyot
Filbertine, Grace
Torvorapanit, Pattama
Wright, Helen L.
Edwards, Steven W.
Leelahavanichkul, Asada
Hirankarn, Nattiya
Chiewchengchol, Direkrit
author_facet Saithong, Supichcha
Saisorn, Wilasinee
Tovichayathamrong, Punyot
Filbertine, Grace
Torvorapanit, Pattama
Wright, Helen L.
Edwards, Steven W.
Leelahavanichkul, Asada
Hirankarn, Nattiya
Chiewchengchol, Direkrit
author_sort Saithong, Supichcha
collection PubMed
description Neutrophil Extracellular Traps (NETs) are a contributing factor of vascular thrombosis and alveolar damage in COVID-19 patients. As enoxaparin is currently used to inhibit vascular thrombosis, this study aimed to investigate whether enoxaparin also reduced inflammation and NETs in COVID-19 patients. Patients with COVID-19 infection were classified into three groups: mild, moderate, and severe (n = 10 for all groups). Plasma was collected from patients and healthy donors (n = 10). Neutrophils isolated from healthy controls were incubated with COVID-19 or healthy plasma, and with or without enoxaparin pretreatment in vitro. Neutrophils and plasma isolated from patients treated with enoxaparin were also investigated. The levels of inflammatory cytokines and NET products such as dsDNA, NE, MPO–DNA and Histone–DNA complexes in plasma and supernatants were measured using immunofluorescence staining and ELISA kits. The expression of inflammatory signaling genes by neutrophils (RELA, SYK, ERK and PKC) was measured using real-time qPCR. The levels of NET products were elevated in the plasma of COVID-19 patients, particularly in the severe group (p < 0.01). Moreover, plasma from the severe group enhanced NET formation (p < 0.01) from neutrophils in vitro. Enoxaparin pretreatment in vitro decreased plasma-induced NETs in a dose-dependent manner and down-regulated the expression of inflammatory genes (p < 0.05). Patients treated with prophylactic enoxaparin showed lower inflammatory cytokine levels and expression of inflammatory genes (p < 0.05). Increased NETs were associated with the severity of COVID-19 infection, particularly in patients with severe pneumonia, and could be used as biomarkers to assess disease severity. Enoxaparin pretreatment inhibited NETs and reduced the expression of inflammatory cytokines, and these effects mostly persisted in patients treated with prophylactic enoxaparin.
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spelling pubmed-91023872022-05-14 Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients Saithong, Supichcha Saisorn, Wilasinee Tovichayathamrong, Punyot Filbertine, Grace Torvorapanit, Pattama Wright, Helen L. Edwards, Steven W. Leelahavanichkul, Asada Hirankarn, Nattiya Chiewchengchol, Direkrit Int J Mol Sci Article Neutrophil Extracellular Traps (NETs) are a contributing factor of vascular thrombosis and alveolar damage in COVID-19 patients. As enoxaparin is currently used to inhibit vascular thrombosis, this study aimed to investigate whether enoxaparin also reduced inflammation and NETs in COVID-19 patients. Patients with COVID-19 infection were classified into three groups: mild, moderate, and severe (n = 10 for all groups). Plasma was collected from patients and healthy donors (n = 10). Neutrophils isolated from healthy controls were incubated with COVID-19 or healthy plasma, and with or without enoxaparin pretreatment in vitro. Neutrophils and plasma isolated from patients treated with enoxaparin were also investigated. The levels of inflammatory cytokines and NET products such as dsDNA, NE, MPO–DNA and Histone–DNA complexes in plasma and supernatants were measured using immunofluorescence staining and ELISA kits. The expression of inflammatory signaling genes by neutrophils (RELA, SYK, ERK and PKC) was measured using real-time qPCR. The levels of NET products were elevated in the plasma of COVID-19 patients, particularly in the severe group (p < 0.01). Moreover, plasma from the severe group enhanced NET formation (p < 0.01) from neutrophils in vitro. Enoxaparin pretreatment in vitro decreased plasma-induced NETs in a dose-dependent manner and down-regulated the expression of inflammatory genes (p < 0.05). Patients treated with prophylactic enoxaparin showed lower inflammatory cytokine levels and expression of inflammatory genes (p < 0.05). Increased NETs were associated with the severity of COVID-19 infection, particularly in patients with severe pneumonia, and could be used as biomarkers to assess disease severity. Enoxaparin pretreatment inhibited NETs and reduced the expression of inflammatory cytokines, and these effects mostly persisted in patients treated with prophylactic enoxaparin. MDPI 2022-04-27 /pmc/articles/PMC9102387/ /pubmed/35563204 http://dx.doi.org/10.3390/ijms23094805 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Saithong, Supichcha
Saisorn, Wilasinee
Tovichayathamrong, Punyot
Filbertine, Grace
Torvorapanit, Pattama
Wright, Helen L.
Edwards, Steven W.
Leelahavanichkul, Asada
Hirankarn, Nattiya
Chiewchengchol, Direkrit
Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients
title Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients
title_full Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients
title_fullStr Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients
title_full_unstemmed Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients
title_short Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients
title_sort anti-inflammatory effects and decreased formation of neutrophil extracellular traps by enoxaparin in covid-19 patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102387/
https://www.ncbi.nlm.nih.gov/pubmed/35563204
http://dx.doi.org/10.3390/ijms23094805
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