scholarly journals COVID-19 Hyperinflammation: What about Neutrophils?

mSphere ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Athanasios Didangelos
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Published Data ◽  
Data Sets ◽  
Rna Seq ◽  
Inflammatory Genes ◽  
Infected Cells ◽  
Neutrophil Response ◽  
Druggable Targets

ABSTRACT COVID-19 is often related to hyperinflammation that drives lung or multiorgan injury. The immunopathological mechanisms that cause excessive inflammation are under investigation and constantly updated. Here, a gene network approach was used on recently published data sets to identify possible COVID-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-CoV-2 cellular receptors led to the mining of a neutrophil-response signature and relevant inflammatory genes. Second, analysis of RNA-seq data sets of lung cells infected with SARS-CoV-2 revealed that infected cells expressed neutrophil-attracting chemokines. Third, analysis of RNA-seq data sets of bronchoalveolar lavage fluid cells from COVID-19 patients identified upregulation of neutrophil genes and chemokines. Different inflammatory genes mined here, including TNFR, IL-8, CXCR1, CXCR2, ADAM10, GPR84, MME, ANPEP, and LAP3, might be druggable targets in efforts to limit SARS-CoV-2 inflammation in severe clinical cases. The possible role of neutrophils in COVID-19 inflammation needs to be studied further.

scholarly journals Neutrophil Involvement in Covid-19

2020 ◽  
Author(s):  
Athanasios Didangelos
Keyword(s):  
Interaction Network ◽  
Lavage Fluid ◽  
Lung Epithelial Cells ◽  
Organ Injury ◽  
Rna Seq ◽  
Protein Protein Interaction ◽  
Associated Proteins ◽  
Infected Cells ◽  
Neutrophil Response

Covid-19 is often related to hyperinflammation that drives lung or multi-organ injury. The immunopathological mechanisms that cause excessive inflammation following SARS-Cov-2 infection are under investigation while different approaches to limit hyperinflammation in affected patients are being proposed. Here, a computational protein-protein interaction network approach was used on recently available data to identify possible Covid-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-Cov-2 cellular receptors and their directly associated proteins, led to the mining of a robust neutrophil response signature and multiple relevant inflammatory genes. Second, analysis of RNA-seq datasets of lung epithelial cells infected with SARS-Cov-2 revealed that infected cells specifically expressed neutrophil-attracting chemokines, further supporting the likely role of neutrophils in Covid-19 inflammation. Third, analysis of RNA-seq datasets of bronchoalveolar lavage fluid from Covid-19 patients, identified neutrophil-specific genes and chemokines. Different immunoregulatory and neutrophil-relevant molecules mined here such as, TNFR, IL8, CXCR1, CXCR2, ADAM10, GPR84, MME-neprilysin, ANPEP and LAP3 are druggable and might be therapeutic targets in efforts to limit SARS-Cov-2 inflammation in severe clinical cases. The role of neutrophils in Covid-19 needs to be studied further.

scholarly journals A Neutrophil Activation Signature in COVID-19

2020 ◽  
Author(s):  
Athanasios Didangelos
Keyword(s):  
Organ Damage ◽  
Lung Epithelial Cells ◽  
Interacting Proteins ◽  
Tnf Receptor ◽  
Rna Seq ◽  
Cellular Receptors ◽  
Lung Epithelial ◽  
Infected Cells ◽  
Neutrophil Response

Covid-19 is often related to hyperinflammation that drives lung or multi-organ damage and mortality. The immunopathological mechanisms that cause excessive inflammation following SARS-Cov-2 infection are under investigation while different approaches to limit hyperinflammation in affected patients are being proposed. Here, a computational network approach was used on recently available data to identify possible Covid-19 inflammatory mechanisms. First, network analysis of putative SARS-Cov-2 cellular receptors and their directly associated interacting proteins, led to the mining of a robust neutrophil-response signature and multiple relevant inflammatory response genes. Second, analysis of RNA-seq datasets of lung epithelial cells infected with SARS-Cov-2 found that infected cells specifically expressed neutrophil-attracting chemokines, further supporting the likely role of neutrophils in Covid-19 inflammation. The role of neutrophils in Covid-19 needs to be studied further. Different immunoregulatory molecules and pathways presented here (TNF Receptor, IL8, CXCR1, CXCR2, ADAM10, GPR84, MME-neprilysin, ANPEP, LAP3) are druggable and might be therapeutic targets in efforts to limit SARS-Cov-2 inflammation in severe clinical cases.

scholarly journals Evidence of a dysregulated Vitamin D pathway in SARS-CoV-2 infected patient’s lung cells

2020 ◽  
Author(s):  
Bijesh George ◽  
Ravikumar Amjesh ◽  
Aswathy Mary Paul ◽  
Madhavan Radhakrishna Pillai ◽  
Rakesh Kumar
Keyword(s):  
Vitamin D ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Differentially Expressed ◽  
Cytokine Signaling ◽  
Lung Cells ◽  
The Status ◽  
Infected Cells ◽  
Cycle Regulation

AbstractAlthough a defective vitamin D pathway has been widely suspected to be associated in SARS-CoV-2 pathobiology, the status of the vitamin D pathway and vitamin D-modulated genes in lung cells of patients infected with SARS-CoV-2 remains unknown. To understand the significance of the vitamin D pathway in SARS-CoV-2 pathobiology, computational approaches were applied to transcriptomic datasets from bronchoalveolar lavage fluid (BALF) cells of such patients or healthy individuals. Levels of vitamin D receptor, retinoid X receptor, and CYP27A1 in BALF cells of patients infected with SARS-CoV-2 were found to be reduced. Additionally, 107 differentially expressed, predominantly downregulated genes modulated by vitamin D were identified in transcriptomic datasets from patient’s cells. Further analysis of differentially expressed genes provided eight novel genes with a conserved motif with vitamin D-responsive elements, implying the role of both direct and indirect mechanisms of gene expression by the dysregulated vitamin D pathway in SARS-CoV-2-infected cells. Network analysis of differentially expressed vitamin D-modulated genes identified pathways in the immune system, NF-κB/cytokine signaling, and cell cycle regulation as top predicted pathways that might be affected in the cells of such patients. In brief, the results provided computational evidence to implicate a dysregulated vitamin D pathway in the pathobiology of SARS-CoV-2 infection.

scholarly journals Crucial Role of Extracellular Vesicles in Bronchial Asthma

2019 ◽  
Vol 20 (10) ◽  
pp. 2589 ◽  
Author(s):  
Tatsuya Nagano ◽  
Masahiro Katsurada ◽  
Ryota Dokuni ◽  
Daisuke Hazama ◽  
Tatsunori Kiriu ◽  
...  
Keyword(s):  
Bronchial Asthma ◽  
Extracellular Vesicles ◽  
Bronchoalveolar Lavage Fluid ◽  
Cell Types ◽  
Lavage Fluid ◽  
Generation Process ◽  
Intracellular Proteins ◽  
Novel Biomarkers ◽  
Microarray Analyses

Extracellular vesicles (EVs) are circulating vesicles secreted by various cell types. EVs are classified into three groups according to size, structural components, and generation process of vesicles: exosomes, microvesicles, and apoptotic bodies. Recently, EVs have been considered to be crucial for cell-to-cell communications and homeostasis because they contain intracellular proteins and nucleic acids. Epithelial cells from mice suffering from bronchial asthma (BA) secrete more EVs and suppress inflammation-induced EV production. Moreover, microarray analyses of bronchoalveolar lavage fluid have revealed that several microRNAs are useful novel biomarkers of BA. Mesenchymal stromal cell-derived EVs are possible candidates of novel BA therapy. In this review, we highlight the biologic roles of EVs in BA and review novel EV-targeted therapy to help understanding by clinicians and biologists.

scholarly journals Role of TNFR1 in the innate airway hyperresponsiveness of obese mice

2012 ◽  
Vol 113 (9) ◽  
pp. 1476-1485 ◽  
Author(s):  
Ming Zhu ◽  
Alison S. Williams ◽  
Lucas Chen ◽  
Allison P. Wurmbrand ◽  
Erin S. Williams ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Tumor Necrosis Factor Receptor ◽  
Lavage Fluid ◽  
Forced Oscillation Technique ◽  
Obese Mice ◽  
Wild Type ◽  
Necrosis Factor

The purpose of this study was to examine the role of tumor necrosis factor receptor 1 (TNFR1) in the airway hyperresponsiveness characteristic of obese mice. Airway responsiveness to intravenous methacholine was measured using the forced oscillation technique in obese Cpe fat mice that were either sufficient or genetically deficient in TNFR1 ( Cpe fat and Cpe fat/TNFR1−/− mice) and in lean mice that were either sufficient or genetically deficient in TNFR1 [wild-type (WT) and TNFR1−/− mice]. Compared with lean WT mice, Cpe fat mice exhibited airway hyperresponsiveness. Airway hyperresponsives was also greater in Cpe fat/TNFR1−/− than in Cpe fat mice. Compared with WT mice, Cpe fat mice had increases in bronchoalveolar lavage fluid concentrations of several inflammatory moieties including eotaxin, IL-9, IP-10, KC, MIG, and VEGF. These factors were also significantly elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice. Additional moieties including IL-13 were also elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice but not in Cpe fat vs. WT mice. IL-17A mRNA expression was greater in Cpe fat/TNFR1−/− vs. Cpe fat mice and in TNFR1−/− vs. WT mice. Analysis of serum indicated that obesity resulted in systemic as well as pulmonary inflammation, but TNFR1 deficiency had little effect on this systemic inflammation. Our results indicate that TNFR1 is protective against the airway hyperresponsiveness associated with obesity and suggest that effects on pulmonary inflammation may be contributing to this protection.

scholarly journals The Role of Thoracic Ultrasonography and Airway Endoscopy in the Diagnosis of Equine Asthma and Exercise-Induced Pulmonary Hemorrhage

2021 ◽  
Vol 8 (11) ◽  
pp. 276
Author(s):  
Chiara Maria Lo Feudo ◽  
Luca Stucchi ◽  
Elena Alberti ◽  
Giovanni Stancari ◽  
Bianca Conturba ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Hemorrhage ◽  
Lavage Fluid ◽  
Lymphoid Hyperplasia ◽  
Inflammatory Status ◽  
Equine Asthma ◽  
Exercise Induced ◽  
Tracheal Mucus ◽  
Tracheal Bifurcation

Mild-moderate (MEA), severe (SEA) equine asthma and exercise-induced pulmonary hemorrhage (EIPH) are common respiratory disorders in horses. The present retrospective study aims to evaluate the role of ultrasonography and endoscopy in the diagnosis of these conditions. Three hundred and three horses were included and divided into SEA, MEA and MEA + EIPH groups, on the basis of history, clinical examination and bronchoalveolar lavage fluid (BALf) cytology; scores were assigned to lung ultrasonography, pharyngeal lymphoid hyperplasia (PLH), tracheal mucus (TM) and tracheal bifurcation edema (TB). These scores were compared between groups, and their associations with age, BALf cytology, tracheal wash microbiology and between endoscopic and ultrasonographic scores were statistically analyzed. Ultrasonographic scores were higher in the SEA and MEA + EIPH groups and associated with increased BALf neutrophils and hemosiderophages. The PLH score was higher in younger horses affected by MEA and EIPH and associated with increased eosinophils and hemosiderophages. TM and TB scores were greater in older horses affected by SEA, associated with increased neutrophils and inversely correlated with hemosiderophages. Moreover, TM grade was negatively correlated with mast cells. Thoracic ultrasonography and airway endoscopy can provide useful information about the inflammatory status of upper and lower airways in the horse.

scholarly journals 2045 The role of TGFβ in driving early cystic fibrosis lung disease

2018 ◽  
Vol 2 (S1) ◽  
pp. 33-33
Author(s):  
Elizabeth L. Kramer ◽  
William Hardie ◽  
Kristin Hudock ◽  
Cynthia Davidson ◽  
Alicia Ostmann ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bronchoalveolar Lavage ◽  
Lung Disease ◽  
Bronchoalveolar Lavage Fluid ◽  
Transforming Growth Factor ◽  
Genetic Modifier ◽  
Lavage Fluid ◽  
Lung Mechanics ◽  
Patient Specific

OBJECTIVES/SPECIFIC AIMS: Transforming growth factor-beta (TGFβ) is a genetic modifier of cystic fibrosis (CF) lung disease. TGFβ’s pulmonary levels in young CF patients and its mechanism of action in CF are unknown. We examined TGFβ levels in children with CF and investigated responses of human airway epithelial cells (AECs) and mice to TGFβ. METHODS/STUDY POPULATION: TGFβ levels in bronchoalveolar lavage fluid from CF patients (n=15) and non-CF control patients (n=21)<6 years old were determined by ELISA. CF mice and non-CF mice were intratracheally treated with an adenoviral TGFβ1 vector or PBS; lungs were collected for analysis at day 7. Human CF and non-CF AECs were treated with TGFβ or PBS for 24 hours then collected for analysis. RESULTS/ANTICIPATED RESULTS: Young CF patients had higher bronchoalveolar lavage fluid TGFβ than non-CF controls (p=0.03). Mouse lungs exposed to TGFβ demonstrated inflammation, goblet cell hyperplasia, and decreased CFTR expression. CF mice had greater TGFβ-induced lung mechanics abnormalities than controls; both CF human AECs and CF mice showed higher TGFβ induced MAPK and PI3K signaling compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: For the first time, we show increased TGFβ levels very early in CF. TGFβ drives CF lung abnormalities in mouse and human models; CF models are more sensitive to TGFβ’s effects. Understanding the role of TGFβ in promoting CF lung disease is critical to developing patient specific treatments.

Interaction of bronchoalveolar lavage fluid with polyplexes and lipoplexes: analysing the role of proteins and glycoproteins

2002 ◽  
Vol 5 (1) ◽  
pp. 49-60 ◽  
Author(s):  
J. Rosenecker ◽  
S. Naundorf ◽  
S. W. Gersting ◽  
R. W. Hauck ◽  
A. Gessner ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid

scholarly journals Role of bronchoalveolar lavage fluid and serum interleukin-27 in the diagnosis of smear-negative pulmonary tuberculosis

Medicine ◽  
2021 ◽  
Vol 100 (20) ◽  
pp. e25821
Author(s):  
Feng Zhu ◽  
Qinfang Ou ◽  
Jian Zheng ◽  
Min Zhou ◽  
Huaxin Chen ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Interleukin 27 ◽  
Smear Negative

scholarly journals An integrative analysis identifying transcriptional features and key genes involved in COVID-19

Epigenomics ◽  
2020 ◽  
Vol 12 (22) ◽  
pp. 1969-1981
Author(s):  
Guoping Li ◽  
Junyi Wang ◽  
Xiang He ◽  
Lei Zhang ◽  
Qin Ran ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Immune Cells ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Integrative Approach ◽  
Molecular Features ◽  
Infected Cells ◽  
Key Genes ◽  
Upregulated Genes ◽  
Core Genes

Aim: To elucidate the transcriptional characteristics of COVID-19. Materials & methods: We utilized an integrative approach to comprehensively analyze the transcriptional features of both COVID-19 patients and SARS-CoV-2 infected cells. Results: Widespread infiltration of immune cells was observed. We identified 233 genes that were codifferentially expressed in both bronchoalveolar lavage fluid and lung samples of COVID-19 patients. Functional analysis suggested upregulated genes were related to immune response such as neutrophil activation and antivirus response, while downregulated genes were associated with cell adhesion. Finally, we identified LCN2, STAT1 and UBE2L6 as core genes during SARS-CoV-2 infection. Conclusion: The identification of core genes involved in COVID-19 can provide us with more insights into the molecular features of COVID-19.

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