Year: 2024
Type: article
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.
Source: Cell Death and Disease
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,790
Funders: U.S. Department of Health and Human Services, Cystic Fibrosis Foundation, Yale University, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences, Yale Liver Center
Awards: G1044130170, G104867962, G143768663, G2137482406, G256819403, G4409303479, Role of Ezrin in Macrophages, G5249776620, G5388098449, G5587623234, G5678777268, G5849466624, Yale Cooperative Center of Excellence in Hematology, The immune regulation of macrophage antibody dependent cellular phagocytosis, G845932970, Pathogenic monocyte response to chronic lung inflammation in cystic fibrosis, BioSystems Networks and Translational Research - Insights into Inflammation (BioSNTR-II), Yale Clinical and Translational Science Award
OpenAlex ID: W4404868366