COVID-19 Pathology Sheds Further Light on Balance between Neutrophil Proteases and Their Inhibitors
Excessive neutrophil influx and activation in lungs during infections, such as manifest during the ongoing SARS CoV-2 pandemic, have brought neutrophil extracellular traps (NETs) and the concomitant release of granule contents that damage surrounding tissues into sharp focus. Neutrophil proteases, w...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/13/1/82 |
| _version_ | 1797445567623725056 |
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| author | Vasuki Silva Marko Radic |
| author_facet | Vasuki Silva Marko Radic |
| author_sort | Vasuki Silva |
| collection | DOAJ |
| description | Excessive neutrophil influx and activation in lungs during infections, such as manifest during the ongoing SARS CoV-2 pandemic, have brought neutrophil extracellular traps (NETs) and the concomitant release of granule contents that damage surrounding tissues into sharp focus. Neutrophil proteases, which are known to participate in NET release, also enable the binding of the viral spike protein to cellular receptors and assist in the spread of infection. Blood and tissue fluids normally also contain liver-derived protease inhibitors that balance the activity of proteases. Interestingly, neutrophils themselves also express the protease inhibitor alpha-1-antitrypsin (AAT), the product of the SERPINA-1 gene, and store it in neutrophil cytoplasmic granules. The absence of AAT or mutations in the SERPINA-1 gene promotes lung remodeling and fibrosis in diseases such as chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS) and increases the risk of allergic responses. Recent observations point to the fact that reduced activity of AAT presents a major susceptibility factor for severe COVID-19. Here, we focus attention on the mechanism of neutrophil elastase (NE) in NET release and its inhibition by AAT as an additional factor that may determine the severity of COVID-19. |
| first_indexed | 2024-03-09T13:27:41Z |
| format | Article |
| id | doaj.art-d7da391b2a144be784cbd4efc101e1c4 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T13:27:41Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-d7da391b2a144be784cbd4efc101e1c42023-11-30T21:22:27ZengMDPI AGBiomolecules2218-273X2022-12-011318210.3390/biom13010082COVID-19 Pathology Sheds Further Light on Balance between Neutrophil Proteases and Their InhibitorsVasuki Silva0Marko Radic1Department of Microbiology, Immunology and Biochemistry, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Microbiology, Immunology and Biochemistry, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USAExcessive neutrophil influx and activation in lungs during infections, such as manifest during the ongoing SARS CoV-2 pandemic, have brought neutrophil extracellular traps (NETs) and the concomitant release of granule contents that damage surrounding tissues into sharp focus. Neutrophil proteases, which are known to participate in NET release, also enable the binding of the viral spike protein to cellular receptors and assist in the spread of infection. Blood and tissue fluids normally also contain liver-derived protease inhibitors that balance the activity of proteases. Interestingly, neutrophils themselves also express the protease inhibitor alpha-1-antitrypsin (AAT), the product of the SERPINA-1 gene, and store it in neutrophil cytoplasmic granules. The absence of AAT or mutations in the SERPINA-1 gene promotes lung remodeling and fibrosis in diseases such as chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS) and increases the risk of allergic responses. Recent observations point to the fact that reduced activity of AAT presents a major susceptibility factor for severe COVID-19. Here, we focus attention on the mechanism of neutrophil elastase (NE) in NET release and its inhibition by AAT as an additional factor that may determine the severity of COVID-19.https://www.mdpi.com/2218-273X/13/1/82alpha-1-antitrypsin (AAT)neutrophil elastase (NE)NETosisPAD4ARDSCOPD |
| spellingShingle | Vasuki Silva Marko Radic COVID-19 Pathology Sheds Further Light on Balance between Neutrophil Proteases and Their Inhibitors Biomolecules alpha-1-antitrypsin (AAT) neutrophil elastase (NE) NETosis PAD4 ARDS COPD |
| title | COVID-19 Pathology Sheds Further Light on Balance between Neutrophil Proteases and Their Inhibitors |
| title_full | COVID-19 Pathology Sheds Further Light on Balance between Neutrophil Proteases and Their Inhibitors |
| title_fullStr | COVID-19 Pathology Sheds Further Light on Balance between Neutrophil Proteases and Their Inhibitors |
| title_full_unstemmed | COVID-19 Pathology Sheds Further Light on Balance between Neutrophil Proteases and Their Inhibitors |
| title_short | COVID-19 Pathology Sheds Further Light on Balance between Neutrophil Proteases and Their Inhibitors |
| title_sort | covid 19 pathology sheds further light on balance between neutrophil proteases and their inhibitors |
| topic | alpha-1-antitrypsin (AAT) neutrophil elastase (NE) NETosis PAD4 ARDS COPD |
| url | https://www.mdpi.com/2218-273X/13/1/82 |
| work_keys_str_mv | AT vasukisilva covid19pathologyshedsfurtherlightonbalancebetweenneutrophilproteasesandtheirinhibitors AT markoradic covid19pathologyshedsfurtherlightonbalancebetweenneutrophilproteasesandtheirinhibitors |