Journal Article

Ezrin drives adaptation of monocytes to the inflamed lung microenvironment

Murray, Thomas S., H Öz, Hasan, Egan, Marie E., Gupta, Neetu, Biancon, Giulia, Cheng, Ee-Chun, Gonzalez, Anjelica L., Huang, Pamela H., Bruscia, Emanuela M., Gudneppanavar, Ravindra, Tebaldi, Toma, Hoppe, Adam D., Di Pietro, Caterina, Halene, Stephanie, Krause, Diane S., Kim, Catherine, Zhang, Ping-Xia

2024

Overview

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.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: 13/2 / 13/31 / 14 / 14/34 / 14/63 / 38 / 38/91 / 45 / 631/250/2504/342/1726 / 631/80/79/750 / 64 / 64/60 / Actin / Adaptation / AKT protein / Animals / Antibodies / Binding sites / Biochemistry / Biomedical and Life Sciences / Bone marrow / Cell activation / Cell Adhesion / Cell Biology / Cell Culture / Cell Differentiation / Cell Proliferation / Cellular Microenvironment / Cystic fibrosis / Cytoskeletal Proteins - genetics / Cytoskeletal Proteins - metabolism / Cytoskeleton / Extracellular matrix / Extracellular Matrix - metabolism / Ezrin / Focal adhesion kinase / Immunology / Infections / Inflammation / Inflammation - metabolism / Inflammation - pathology / Kinases / Leukocyte migration / Life Sciences / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Lung - metabolism / Lung - pathology / Lung diseases / Lungs / Macrophages / Macrophages - metabolism / Medicine / Mice / Mice, Inbred C57BL / Mice, Knockout / Microenvironments / Monocytes / Monocytes - metabolism / Protein-serine/threonine kinase / Proteins / Signal Transduction / T cell receptors