Neutrophil Extracellular Trap Formation Potential Correlates with Lung Disease Severity in COVID-19 Patients

Kinnare, Nedha; Hook, Jessica S.; Patel, Pujan; Monson, Nancy; Moreland, Jessica G.

doi:10.1007/s10753-021-01585-x

Cited by 19 publications

(25 citation statements)

References 57 publications

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“…As in numerous other NETopathies, 3 , 4 , 16 those by‐products may also induce hypertension, thrombosis and vasculitis. 5 , 7 , 15 , 17 In relative concordance with our observations which differentiated NS and S cohorts using NET markers levels, 0/26 and 6/44 (13.6%) patients experienced GI bleeding in NS and S patients, respectively. In addition, levels of ferritin, creatine kinase (CK), lactate dehydrogenase (LDH), CRP, polymorphonucleic cell % (PNN), and d ‐dimers on the one hand, and calcium, lymphocytes to neutrophils ratio (LNR) on the other hand, showed positive and negative associations, respectively, with NE, MPO, and cir‐nDNA levels in the NS and S cohorts (Supporting Information: Figure 1S ).…”

Section: Resultssupporting

confidence: 89%

Persistence of neutrophil extracellular traps and anticardiolipin auto‐antibodies in post‐acute phase COVID‐19 patients

Pisareva

Badiou

Mihalovičová

et al. 2022

Journal of Medical Virology

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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Section: Resultssupporting

confidence: 89%

Persistence of neutrophil extracellular traps and anticardiolipin auto‐antibodies in post‐acute phase COVID‐19 patients

Pisareva

Badiou

Mihalovičová

et al. 2022

Journal of Medical Virology

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“…Altogether, these and our results sustain the hypothesis of a central role for IL-8, in addition to IL-6, in the response of the alveolar epithelium to SARS-CoV-2 infection. This chemokine, deeply involved in neutrophil recruitment and degranulation [37,38], may contribute to lung pathology in COVID-19; indeed, it has been recently shown that the activation of neutrophils upon SARS-CoV-2 infection contributes to tissue injury by causing reactive oxygen species production, granule exocytosis with release of proteases, neutrophil extracellular trap (NET) formation, and release of cytokines [39].…”

Section: Discussionmentioning

confidence: 99%

Immune-Mediated Inflammatory Responses of Alveolar Epithelial Cells: Implications for COVID-19 Lung Pathology

et al. 2022

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Background. Clinical and experimental evidence point to a dysregulated immune response caused by SARS-CoV-2 as the primary mechanism of lung disease in COVID-19. However, the pathogenic mechanisms underlying COVID-19-associated ARDS (Acute Respiratory Distress Syndrome) remain incompletely understood. This study aims to explore the inflammatory responses of alveolar epithelial cells to either the spike S1 protein or to a mixture of cytokines secreted by S1-activated macrophages. Methods and Results. The exposure of alveolar A549 cells to supernatants from spike-activated macrophages caused a further release of inflammatory mediators, with IL-8 reaching massive concentrations. The investigation of the molecular pathways indicated that NF-kB is involved in the transcription of IP-10 and RANTES, while STATs drive the expression of all the cytokines/chemokines tested, with the exception of IL-8 which is regulated by AP-1. Cytokines/chemokines produced by spike-activated macrophages are also likely responsible for the observed dysfunction of barrier integrity in Human Alveolar Epithelial Lentivirus-immortalized cells (hAELVi), as demonstrated by an increased permeability of the monolayers to mannitol, a marked decrease of TEER and a disorganization of claudin-7 distribution. Conclusion. Upon exposure to supernatants from S1-activated macrophages, A549 cells act both as targets and sources of cytokines/chemokines, suggesting that alveolar epithelium along with activated macrophages may orchestrate lung inflammation and contribute to alveolar injury, a hallmark of ARDS.

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“…They can quickly migrate to the inflammatory site and digest and destroy the invading pathogenic microorganisms (Nauseef and Borregaard, 2014;Leiding, 2017). Some studies have demonstrated neutrophils exert an important part in the pathogenesis of ALI (Chen et al, 2018;Tsai et al, 2018;Kinnare et al, 2022). Neutrophils play a core role in the initiation, propagation, and resolution of this complex inflammatory environment by migrating to the lungs and performing various proinflammatory functions.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury

et al. 2022

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Qing-Jin-Hua-Tan-Decoction (QJHTD), a classic famous Chinese ancient prescription, has been used for treatment of pulmonary diseases since Ming Dynasty. A total of 22 prototype compounds of QJHTD absorbed into rat blood were chosen as candidates for the pharmacological network analysis and molecular docking. The targets from the intersection of compound target and ALI disease targets were used for GO and KEGG enrichment analyses. Molecular docking was adopted to further verify the interactions between 22 components and the top 20 targets with higher degree values in the component–target–pathway network. In vitro experiments were performed to verify the results of network pharmacology using SPR experiments, Western blot experiments, and the PMA-induced neutrophils to produce neutrophil extracellular trap (NET) model. The compound–target–pathway network includes 176 targets and 20 signaling pathways in which the degree of MAPK14, CDK2, EGFR, F2, SRC, and AKT1 is higher than that of other targets and which may be potential disease targets. The biological processes in QJHTD for ALI mainly included protein phosphorylation, response to wounding, response to bacterium, regulation of inflammatory response, and so on. KEGG enrichment analyses revealed multiple signaling pathways, including lipid and atherosclerosis, HIF-1 signaling pathway, renin–angiotensin system, and neutrophil extracellular trap formation. The molecular docking results showed that baicalin, oroxylin A-7-glucuronide, hispidulin-7-O-β-D-glucuronide, wogonoside, baicalein, wogonin, tianshic acid, and mangiferin can be combined with most of the targets, which might be the core components of QJHTD in treatment of ALI. Direct binding ability of baicalein, wogonin, and baicalin to thrombin protein was all micromolar, and their KD values were 11.92 μM, 1.303 μM, and 1.146 μM, respectively, revealed by SPR experiments, and QJHTD could inhibit Src phosphorylation in LPS-activated neutrophils by Western blot experiments. The experimental results of PMA-induced neutrophils to produce NETs indicated that QJHTD could inhibit the production of NETs. This study revealed the active compounds, effective targets, and potential pharmacological mechanisms of QJHTD acting on ALI.

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Neutrophil Extracellular Trap Formation Potential Correlates with Lung Disease Severity in COVID-19 Patients

Cited by 19 publications

References 57 publications

Persistence of neutrophil extracellular traps and anticardiolipin auto‐antibodies in post‐acute phase COVID‐19 patients

Persistence of neutrophil extracellular traps and anticardiolipin auto‐antibodies in post‐acute phase COVID‐19 patients

Immune-Mediated Inflammatory Responses of Alveolar Epithelial Cells: Implications for COVID-19 Lung Pathology

Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury

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