Ezrin drives adaptation of monocytes to the inflamed lung microenvironment
Abstract Ezrin, an actin-binding protein, orchestrates the organization of the cortical cytoskeleton and plasma membrane during cell migration, adhesion, and proliferation. Its role in monocytes/macrophages (MΦs) is less understood. Here, we used a monocyte/MΦ-specific ezrin knock-out mouse model to...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-024-07255-8 |
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| author | Ravindra Gudneppanavar Caterina Di Pietro Hasan H Öz Ping-Xia Zhang Ee-Chun Cheng Pamela H. Huang Toma Tebaldi Giulia Biancon Stephanie Halene Adam D. Hoppe Catherine Kim Anjelica L. Gonzalez Diane S. Krause Marie E. Egan Neetu Gupta Thomas S. Murray Emanuela M. Bruscia |
| author_facet | Ravindra Gudneppanavar Caterina Di Pietro Hasan H Öz Ping-Xia Zhang Ee-Chun Cheng Pamela H. Huang Toma Tebaldi Giulia Biancon Stephanie Halene Adam D. Hoppe Catherine Kim Anjelica L. Gonzalez Diane S. Krause Marie E. Egan Neetu Gupta Thomas S. Murray Emanuela M. Bruscia |
| author_sort | Ravindra Gudneppanavar |
| collection | DOAJ |
| description | Abstract Ezrin, an actin-binding protein, orchestrates the organization of the cortical cytoskeleton and plasma membrane during cell migration, adhesion, and proliferation. Its role in monocytes/macrophages (MΦs) is less understood. Here, we used a monocyte/MΦ-specific ezrin knock-out mouse model to investigate the contribution of ezrin to monocyte recruitment and adaptation to the lung extracellular matrix (ECM) in response to lipopolysaccharide (LPS). Our study revealed that LPS induces ezrin expression in monocytes/MΦs and is essential for monocytes to adhere to lung ECM, proliferate, and differentiate into tissue-resident interstitial MΦs. Mechanistically, the loss of ezrin in monocytes disrupts activation of focal adhesion kinase and AKT serine-threonine protein kinase signaling, essential for lung-recruited monocytes and monocyte-derived MΦs to adhere to the ECM, proliferate, and survive. In summary, our data show that ezrin plays a role beyond structural cellular support, influencing diverse monocytes/MΦ processes and signaling pathways during inflammation, facilitating their differentiation into tissue-resident macrophages. |
| format | Article |
| id | doaj-art-a14808cb3fb24df6a2ce87b009fee579 |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-a14808cb3fb24df6a2ce87b009fee5792025-08-20T02:49:16ZengNature Publishing GroupCell Death and Disease2041-48892024-11-01151111710.1038/s41419-024-07255-8Ezrin drives adaptation of monocytes to the inflamed lung microenvironmentRavindra Gudneppanavar0Caterina Di Pietro1Hasan H Öz2Ping-Xia Zhang3Ee-Chun Cheng4Pamela H. Huang5Toma Tebaldi6Giulia Biancon7Stephanie Halene8Adam D. Hoppe9Catherine Kim10Anjelica L. Gonzalez11Diane S. Krause12Marie E. Egan13Neetu Gupta14Thomas S. Murray15Emanuela M. Bruscia16Department of Pediatrics, School of Medicine, Yale UniversityDepartment of Pediatrics, School of Medicine, Yale UniversityDepartment of Pediatrics, School of Medicine, Yale UniversityDepartment of Pediatrics, School of Medicine, Yale UniversityDepartment of Pediatrics, School of Medicine, Yale UniversityDepartment of Pediatrics, School of Medicine, Yale UniversityYale Stem Cell Center, School of Medicine, Yale UniversityYale Stem Cell Center, School of Medicine, Yale UniversityYale Stem Cell Center, School of Medicine, Yale UniversityDepartment of Chemistry and Biochemistry, South Dakota State UniversityDepartment of Biomedical Engineering, Yale UniversityDepartment of Biomedical Engineering, Yale UniversityYale Stem Cell Center, School of Medicine, Yale UniversityDepartment of Pediatrics, School of Medicine, Yale UniversityDepartment of Inflammation and Immunity, Cleveland Clinic FoundationDepartment of Pediatrics, School of Medicine, Yale UniversityDepartment of Pediatrics, School of Medicine, Yale UniversityAbstract Ezrin, an actin-binding protein, orchestrates the organization of the cortical cytoskeleton and plasma membrane during cell migration, adhesion, and proliferation. Its role in monocytes/macrophages (MΦs) is less understood. Here, we used a monocyte/MΦ-specific ezrin knock-out mouse model to investigate the contribution of ezrin to monocyte recruitment and adaptation to the lung extracellular matrix (ECM) in response to lipopolysaccharide (LPS). Our study revealed that LPS induces ezrin expression in monocytes/MΦs and is essential for monocytes to adhere to lung ECM, proliferate, and differentiate into tissue-resident interstitial MΦs. Mechanistically, the loss of ezrin in monocytes disrupts activation of focal adhesion kinase and AKT serine-threonine protein kinase signaling, essential for lung-recruited monocytes and monocyte-derived MΦs to adhere to the ECM, proliferate, and survive. In summary, our data show that ezrin plays a role beyond structural cellular support, influencing diverse monocytes/MΦ processes and signaling pathways during inflammation, facilitating their differentiation into tissue-resident macrophages.https://doi.org/10.1038/s41419-024-07255-8 |
| spellingShingle | Ravindra Gudneppanavar Caterina Di Pietro Hasan H Öz Ping-Xia Zhang Ee-Chun Cheng Pamela H. Huang Toma Tebaldi Giulia Biancon Stephanie Halene Adam D. Hoppe Catherine Kim Anjelica L. Gonzalez Diane S. Krause Marie E. Egan Neetu Gupta Thomas S. Murray Emanuela M. Bruscia Ezrin drives adaptation of monocytes to the inflamed lung microenvironment Cell Death and Disease |
| title | Ezrin drives adaptation of monocytes to the inflamed lung microenvironment |
| title_full | Ezrin drives adaptation of monocytes to the inflamed lung microenvironment |
| title_fullStr | Ezrin drives adaptation of monocytes to the inflamed lung microenvironment |
| title_full_unstemmed | Ezrin drives adaptation of monocytes to the inflamed lung microenvironment |
| title_short | Ezrin drives adaptation of monocytes to the inflamed lung microenvironment |
| title_sort | ezrin drives adaptation of monocytes to the inflamed lung microenvironment |
| url | https://doi.org/10.1038/s41419-024-07255-8 |
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