Cited by 235Inflammasome and immune disordersCOVID-19 Clinical Research StudiesAutoimmune and Inflammatory Disorders Research

The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.

SARS-CoV-2 infection and overactivation of Nlrp3 inflammasome as a trigger of cytokine “storm” and risk factor for damage of hematopoietic stem cells

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Abstract

The scientific community faces an unexpected and urgent challenge related to the SARS-CoV-2 pandemic and is investigating the role of receptors involved in entry of this virus into cells as well as pathomechanisms leading to a cytokine “storm,” which in many cases ends in severe acute respiratory syndrome, fulminant myocarditis and kidney injury. An important question is if it may also damage hematopoietic stem progenitor cells?

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Crossref · 10.1038/s41375-020-0887-9

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Fig. 1 The pathways of Nlrp3 inflammasome activation in response to SARS-CoV-2 infection that may lead to initiation of cytokine storm and pyroptosis in cells including HSPCs. a It is possible that, by binding to ACE2 via the spike protein, SARS-CoV-2 directly activates the Nlrp3 inflammasome. This possibility is currently being investigated by our team. b Activation of the renin–angiotensin–aldosterone system (RAAS) leads to elevated levels of angiotensin II, which, after binding to the AT1 receptor, activates the Nlrp3 inflammasome in target cells. c Finally, the N proteins of the SARS-CoV-2 virus may activate the ComC in an MBL–MASP-2-dependent manner, and the ComC cleavage fragments (the C3a and C5a anaphylatoxins), as well as the C5b/C9 membrane attack complex (MAC), may additionally activate the Nlrp3 inflammasome in cells. (Of note, MASP-2 also activates the coagulation cascade by converting prothrombin into thrombin). Overall, activation of all three of these pathways leads to activation of caspase 1, the release of the mature IL-1β and IL-18 cytokines, the insertion of gasdermin D channels in the cell membrane, and the release of danger-associated molecular pattern molecules (DAMPs), which amplify the innate immune response and may lead to cell death by pyroptosis.
Fig. 1 The pathways of Nlrp3 inflammasome activation in response to SARS-CoV-2 infection that may lead to initiation of cytokine storm and pyroptosis in cells including HSPCs. a It is possible that, by binding to ACE2 via the spike protein, SARS-CoV-2 directly activates the Nlrp3 inflammasome. This possibility is currently being investigated by our team. b Activation of the renin–angiotensin–aldosterone system (RAAS) leads to elevated levels of angiotensin II, which, after binding to the AT1 receptor, activates the Nlrp3 inflammasome in target cells. c Finally, the N proteins of the SARS-CoV-2 virus may activate the ComC in an MBL–MASP-2-dependent manner, and the ComC cleavage fragments (the C3a and C5a anaphylatoxins), as well as the C5b/C9 membrane attack complex (MAC), may additionally activate the Nlrp3 inflammasome in cells. (Of note, MASP-2 also activates the coagulation cascade by converting prothrombin into thrombin). Overall, activation of all three of these pathways leads to activation of caspase 1, the release of the mature IL-1β and IL-18 cytokines, the insertion of gasdermin D channels in the cell membrane, and the release of danger-associated molecular pattern molecules (DAMPs), which amplify the innate immune response and may lead to cell death by pyroptosis.CC BY · PubMed Central

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Metadata

Authors
Ratajczak, M. Z., & Kucia, M.
Affiliations
University of Louisville (US)
Corresponding author
Ratajczak, Mariusz Z.
Venue
Leukemia
Published
2020-06-01
Volume
34
Issue
7
Pages
1726-1729
ISSN
  • 0887-6924 (ISSN-L)
  • 1476-5551
OpenAlex
W3031438965
Cited by
235
References
16
Citations by year
2026: 7 · 2025: 17 · 2024: 26 · 2023: 26 · 2022: 57 · 2021: 69 · 2020: 33
FWCI
15.09
Type
journal article
Language
en
Open access
Locations
  • Leukemia (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (2R01 DK074720)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Keywords
SARS-CoV-2, NLRP3 inflammasome, cytokine storm, hematopoietic stem cells, COVID-19 pathogenesis, myocarditis, kidney injury, viral entry receptor
MeSH terms
Pyroptosis, NLR Family, Pyrin Domain-Containing 3 Protein, Betacoronavirus, Cytokine Release Syndrome, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Furans, Gene Expression Regulation, Hematopoietic Stem Cells, Heterocyclic Compounds, 4 or More Rings, Humans, Immunity, Innate, Immunologic Factors, Indenes, Peptidyl-Dipeptidase A, Myocarditis, Pneumonia, Viral, Risk Factors, Sulfonamides, Sulfones, T-Lymphocytes, Cytokines, Coronavirus Infections, Severe Acute Respiratory Syndrome, Acute Kidney Injury, Inflammasomes, Pandemics, Spike Glycoprotein, Coronavirus

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