Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?
Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13533 |
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| author | Maura D’Amato Monica Campagnoli Paolo Iadarola Paola Margherita Bignami Marco Fumagalli Laurent Roberto Chiarelli Giovanni Stelitano Federica Meloni Pasquale Linciano Simona Collina Giampiero Pietrocola Valentina Vertui Anna Aliberti Tommaso Fossali Simona Viglio |
| author_facet | Maura D’Amato Monica Campagnoli Paolo Iadarola Paola Margherita Bignami Marco Fumagalli Laurent Roberto Chiarelli Giovanni Stelitano Federica Meloni Pasquale Linciano Simona Collina Giampiero Pietrocola Valentina Vertui Anna Aliberti Tommaso Fossali Simona Viglio |
| author_sort | Maura D’Amato |
| collection | DOAJ |
| description | Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE–AAT) in which the two proteins are covalently bound. The lack of this complex, together with the detection of HNE activity in BALf/plasma samples of COVID-19 patients, leads us to hypothesize that potential functional deficiencies should necessarily be attributed to possible structural modifications of AAT. These could greatly diminish its ability to inhibit neutrophil elastase, thus reducing lung protection. The aim of this work was to explore the oxidation state of AAT in BALf/plasma samples from these patients so as to understand whether the deficient inhibitory activity of AAT was somehow related to possible conformational changes caused by the presence of abnormally oxidized residues. |
| first_indexed | 2024-03-10T23:21:03Z |
| format | Article |
| id | doaj.art-f969aa926fc24a748b146b9e4fec0de3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:21:03Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f969aa926fc24a748b146b9e4fec0de32023-11-19T08:18:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171353310.3390/ijms241713533Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?Maura D’Amato0Monica Campagnoli1Paolo Iadarola2Paola Margherita Bignami3Marco Fumagalli4Laurent Roberto Chiarelli5Giovanni Stelitano6Federica Meloni7Pasquale Linciano8Simona Collina9Giampiero Pietrocola10Valentina Vertui11Anna Aliberti12Tommaso Fossali13Simona Viglio14Department of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnologies “L. Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnologies “L. Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnologies “L. Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnologies “L. Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnologies “L. Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, 27100 Pavia, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyDepartment of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, ItalyDivision of Anesthesiology and Intensive Care 1, IRCCS Policlinico San Matteo, 27100 Pavia, ItalyDepartment of Anesthesiology and Intensive Care, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, 20157 Milan, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyHuman neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE–AAT) in which the two proteins are covalently bound. The lack of this complex, together with the detection of HNE activity in BALf/plasma samples of COVID-19 patients, leads us to hypothesize that potential functional deficiencies should necessarily be attributed to possible structural modifications of AAT. These could greatly diminish its ability to inhibit neutrophil elastase, thus reducing lung protection. The aim of this work was to explore the oxidation state of AAT in BALf/plasma samples from these patients so as to understand whether the deficient inhibitory activity of AAT was somehow related to possible conformational changes caused by the presence of abnormally oxidized residues.https://www.mdpi.com/1422-0067/24/17/13533lungα1-antitrypsin (AAT)human neutrophil elastase (HNE)COVID-19SARS-CoV-2broncho-alveolar lavage (BAL) |
| spellingShingle | Maura D’Amato Monica Campagnoli Paolo Iadarola Paola Margherita Bignami Marco Fumagalli Laurent Roberto Chiarelli Giovanni Stelitano Federica Meloni Pasquale Linciano Simona Collina Giampiero Pietrocola Valentina Vertui Anna Aliberti Tommaso Fossali Simona Viglio Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients? International Journal of Molecular Sciences lung α1-antitrypsin (AAT) human neutrophil elastase (HNE) COVID-19 SARS-CoV-2 broncho-alveolar lavage (BAL) |
| title | Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients? |
| title_full | Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients? |
| title_fullStr | Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients? |
| title_full_unstemmed | Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients? |
| title_short | Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients? |
| title_sort | could the oxidation of α1 antitrypsin prevent the binding of human neutrophil elastase in covid 19 patients |
| topic | lung α1-antitrypsin (AAT) human neutrophil elastase (HNE) COVID-19 SARS-CoV-2 broncho-alveolar lavage (BAL) |
| url | https://www.mdpi.com/1422-0067/24/17/13533 |
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