Autophagy Protects against Eosinophil Cytolysis and Release of DNA
The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Eosinophils deposit their damaging products in airway tissue, likely by degranulation and cytolysis. We previously showed that priming blood eosinophils with IL3 strongly increased their cytolysis...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/11/1821 |
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| author | Stephane Esnault Paul S. Fichtinger Karina T. Barretto Frances J. Fogerty Ksenija Bernau Deane F. Mosher Sameer K. Mathur Nathan Sandbo Nizar N. Jarjour |
| author_facet | Stephane Esnault Paul S. Fichtinger Karina T. Barretto Frances J. Fogerty Ksenija Bernau Deane F. Mosher Sameer K. Mathur Nathan Sandbo Nizar N. Jarjour |
| author_sort | Stephane Esnault |
| collection | DOAJ |
| description | The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Eosinophils deposit their damaging products in airway tissue, likely by degranulation and cytolysis. We previously showed that priming blood eosinophils with IL3 strongly increased their cytolysis on aggregated IgG. Conversely, IL5 priming did not result in significant eosinophil cytolysis in the same condition. Therefore, to identify critical events protecting eosinophils from cell cytolysis, we examined the differential intracellular events between IL5- and IL3-primed eosinophils interacting with IgG. We showed that both IL3 and IL5 priming increased the eosinophil adhesion to IgG, phosphorylation of p38, and production of reactive oxygen species (ROS), and decreased the phosphorylation of cofilin. However, autophagic flux as measured by the quantification of SQSTM1-p62 and lipidated-MAP1L3CB over time on IgG, with or without bafilomycin-A1, was higher in IL5-primed compared to IL3-primed eosinophils. In addition, treatment with bafilomycin-A1, an inhibitor of granule acidification and autophagolysosome formation, enhanced eosinophil cytolysis and DNA trap formation in IL5-primed eosinophils. Therefore, this study suggests that increased autophagy in eosinophils protects from cytolysis and the release of DNA, and thus limits the discharge of damaging intracellular eosinophilic contents. |
| first_indexed | 2024-03-10T01:24:35Z |
| format | Article |
| id | doaj.art-242f93c7f71443118998f4a3460d1fd0 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:24:35Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-242f93c7f71443118998f4a3460d1fd02023-11-23T13:53:19ZengMDPI AGCells2073-44092022-06-011111182110.3390/cells11111821Autophagy Protects against Eosinophil Cytolysis and Release of DNAStephane Esnault0Paul S. Fichtinger1Karina T. Barretto2Frances J. Fogerty3Ksenija Bernau4Deane F. Mosher5Sameer K. Mathur6Nathan Sandbo7Nizar N. Jarjour8Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USADivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USADepartment of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USADepartment of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USADivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USADepartment of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USADivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USADivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USADivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USAThe presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Eosinophils deposit their damaging products in airway tissue, likely by degranulation and cytolysis. We previously showed that priming blood eosinophils with IL3 strongly increased their cytolysis on aggregated IgG. Conversely, IL5 priming did not result in significant eosinophil cytolysis in the same condition. Therefore, to identify critical events protecting eosinophils from cell cytolysis, we examined the differential intracellular events between IL5- and IL3-primed eosinophils interacting with IgG. We showed that both IL3 and IL5 priming increased the eosinophil adhesion to IgG, phosphorylation of p38, and production of reactive oxygen species (ROS), and decreased the phosphorylation of cofilin. However, autophagic flux as measured by the quantification of SQSTM1-p62 and lipidated-MAP1L3CB over time on IgG, with or without bafilomycin-A1, was higher in IL5-primed compared to IL3-primed eosinophils. In addition, treatment with bafilomycin-A1, an inhibitor of granule acidification and autophagolysosome formation, enhanced eosinophil cytolysis and DNA trap formation in IL5-primed eosinophils. Therefore, this study suggests that increased autophagy in eosinophils protects from cytolysis and the release of DNA, and thus limits the discharge of damaging intracellular eosinophilic contents.https://www.mdpi.com/2073-4409/11/11/1821eosinophilsautophagycytolysisDNA trapsSQSTM1MAP1LC3B |
| spellingShingle | Stephane Esnault Paul S. Fichtinger Karina T. Barretto Frances J. Fogerty Ksenija Bernau Deane F. Mosher Sameer K. Mathur Nathan Sandbo Nizar N. Jarjour Autophagy Protects against Eosinophil Cytolysis and Release of DNA Cells eosinophils autophagy cytolysis DNA traps SQSTM1 MAP1LC3B |
| title | Autophagy Protects against Eosinophil Cytolysis and Release of DNA |
| title_full | Autophagy Protects against Eosinophil Cytolysis and Release of DNA |
| title_fullStr | Autophagy Protects against Eosinophil Cytolysis and Release of DNA |
| title_full_unstemmed | Autophagy Protects against Eosinophil Cytolysis and Release of DNA |
| title_short | Autophagy Protects against Eosinophil Cytolysis and Release of DNA |
| title_sort | autophagy protects against eosinophil cytolysis and release of dna |
| topic | eosinophils autophagy cytolysis DNA traps SQSTM1 MAP1LC3B |
| url | https://www.mdpi.com/2073-4409/11/11/1821 |
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