Calprotectin in Lung Diseases

Kotsiou, Ourania S.; Papagiannis, Dimitrios; Papadopoulou, Rodanthi; Gourgoulianis, Konstantinos

doi:10.3390/ijms22041706

Cited by 34 publications

(32 citation statements)

References 204 publications

(351 reference statements)

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“…In this study, they used high-dimensional flow cytometry and single-cell RNA sequencing of COVID-19 peripheral blood and suggested that high calprotectin production is mediated by abnormal myeloid subsets [ 54 ]. Calprotectin genes are also expressed in lungs, particularly in lung epithelial and alveolar type II pneumocytes [ 55 ]. Likewise, the expression of these genes is increased with viral infection [ 56 ] and lipopolysaccharide stimulation [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of oxidative stress gene markers during SARS-COV-2 viral infection

Sharif-Askari

Mdkhana

et al. 2021

Free Radical Biology and Medicine

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Severe viral infections, including SARS-COV-2, could trigger disruption of the balance between pro-oxidant and antioxidant mediators; the magnitude of which could reflect the severity of infection and lung injury. Using publicly available COVID-19 transcriptomic datasets, we conducted an in-silico analyses to evaluate the expression levels of 125 oxidative stress genes, including 37 pro-oxidant genes, 32 oxidative-responsive genes, and 56 antioxidant genes. Seven oxidative stress genes were found to be upregulated in whole blood and lung autopsies (MPO, S100A8, S100A9, SRXN1, GCLM, SESN2, and TXN); these genes were higher in severe versus non-severe COVID-19 leucocytes. Oxidative genes were upregulated in inflammatory cells comprising macrophages and CD8 + T cells isolated from bronchioalveolar fluid (BALF), and neutrophils isolated from peripheral blood. MPO, S100A8, and S100A9 were t/opmost upregulated oxidative markers within COVID-19's lung autopsies, whole blood, leucocytes, BALF derived macrophages and circulating neutrophils. The calprotectin's, S100A8 and S100A9 were upregulated in SARS-COV-2 infected human lung epithelium. To validate our in-silico analysis, we conducted qRT-PCR to measure MPO and calprotectin's levels in blood and saliva samples. Relative to uninfected donor controls, MPO, S100A8 and S100A9 were significantly higher in blood and saliva of severe versus asymptomatic COVID-19 patients. Compared to other different viral respiratory infections, coronavirus infection showed a prominent upregulation in oxidative stress genes with MPO and calprotectin at the top of the list. In conclusion, SARS-COV-2 induce the expression of oxidative stress genes via both immune as well as lung structural cells. The observed correlation between oxidative stress genes dysregulation and COVID-19 disease severity deserve more attention. Mechanistical studies are required to confirm the correlation between oxidative stress gene dysregulation, COVID-19 severity, and the net oxidative stress balance.

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Section: Discussionmentioning

confidence: 99%

Upregulation of oxidative stress gene markers during SARS-COV-2 viral infection

Sharif-Askari

Mdkhana

et al. 2021

Free Radical Biology and Medicine

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“…S100A8 and S100A9 form a heterodimer complex called Calprotectin (CLP). Elevated levels of CLP is found in bronchoalveolar lavage fluid (BALF), serum and lung tissue of pneumonia patients 23 . Serum CLP could be potential biomarker for COVID-19 and further research is required to test this hypothesis 24 .…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptome analyses reveal genes associated with SARS-CoV-2 infection of human lung epithelial cells

Chandrashekar

Athar

Manne

et al. 2021

Sci Rep

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During 2020, understanding the molecular mechanism of SARS-CoV-2 infection (the cause of COVID-19) became a scientific priority due to the devastating effects of the COVID-19. Many researchers have studied the effect of this viral infection on lung epithelial transcriptomes and deposited data in public repositories. Comprehensive analysis of such data could pave the way for development of efficient vaccines and effective drugs. In the current study, we obtained high-throughput gene expression data associated with human lung epithelial cells infected with respiratory viruses such as SARS-CoV-2, SARS, H1N1, avian influenza, rhinovirus and Dhori, then performed comparative transcriptome analysis to identify SARS-CoV-2 exclusive genes. The analysis yielded seven SARS-CoV-2 specific genes including CSF2 [GM-CSF] (colony-stimulating factor 2) and calcium-binding proteins (such as S100A8 and S100A9), which are known to be involved in respiratory diseases. The analyses showed that genes involved in inflammation are commonly altered by infection of SARS-CoV-2 and influenza viruses. Furthermore, results of protein–protein interaction analyses were consistent with a functional role of CSF2 and S100A9 in COVID-19 disease. In conclusion, our analysis revealed cellular genes associated with SARS-CoV-2 infection of the human lung epithelium; these are potential therapeutic targets.

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“…The upregulation of calprotectin expression has been associated with various inflammatory processes such as inflammatory bowel disease, rheumatoid arthritis, spondyloarthritis and cardiovascular disease in type 2 diabetes mellitus (6)(7)(8)(9). Additionally, calprotectin is crucial for neutrophil accumulation and inflammation in the lung parenchyma during bacterial community acquired pneumonia (10).…”

Section: Discussionmentioning

confidence: 99%

IL-1 Mediates Tissue Specific Inflammation and Severe Respiratory Failure In Covid-19: Clinical And Experimental Evidence

Renieris¹,

Karakike²,

Gkavogianni³

et al. 2021

Preprint

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Background: Acute respiratory distress syndrome (ARDS) in COVID-19 has been associated with dysregulated immune responses leading to catastrophic inflammation. The activation pathways remain to be fully elucidated. We investigated the ability of circulating to induce dysregulated immune responses. Materials & Methods: Calprotectin and high mobility group box 1 (HMGB1) were associated with ARDS in 60 COVID-19 patients. In a second cohort of 40 COVID-19 patients calprotectin at hospital admission was associated with serum levels of soluble urokinase plasminogen activator receptor (suPAR). A COVID-19 animal model was developed by intravenous injection of plasma from healthy volunteers or patients with COVID-19 ARDS into C57/BL6 mice once daily for 3 consecutive days. In separate experiments, mice were treated with a) the IL-1 receptor antagonist Anakinra or vehicle and b) Flo1-2a anti-murine anti-IL-1α monoclonal antibody or the specific anti-human IL-1α antibody XB2001, or isotype controls. Mice were sacrificed on day 4. Cytokines and myeloperoxidase (MPO) in tissues were measured. Results: Calprotectin, but not HMGB1, was elevated ARDS. Higher suPAR readouts indicated higher calprotectin levels. CHallenge of mice with COVID-19 plasma led to inflammatory reactions in murine lung and intestines as evidenced by increased levels of TNFα, IL-6, IFNγ and MPO. Anakinra treatment brought these levels down. Similar decrease was found in mice treated with Flo1-2a but not with XB2001. Conclusion: Circulating alarmins, specifically calprotectin, of critically ill COVID-19 patients induces tissue-specific inflammatory responses through an IL-1α mediated mechanism. This could be attenuated through inhibition of IL-1 receptor or specific inhibition of IL-1α.

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Calprotectin in Lung Diseases

Cited by 34 publications

References 204 publications

Upregulation of oxidative stress gene markers during SARS-COV-2 viral infection

Upregulation of oxidative stress gene markers during SARS-COV-2 viral infection

Comparative transcriptome analyses reveal genes associated with SARS-CoV-2 infection of human lung epithelial cells

IL-1 Mediates Tissue Specific Inflammation and Severe Respiratory Failure In Covid-19: Clinical And Experimental Evidence

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