Department of Pediatrics, School of Medicine, Yale University, New Haven, CT, USA.
Yale Stem Cell Center, School of Medicine, Yale University, New Haven, CT, USA.
Cell Death Dis. 2024 Nov 29;15(11):864. doi: 10.1038/s41419-024-07255-8.
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.
埃兹蛋白是一种肌动蛋白结合蛋白，在细胞迁移、黏附和增殖过程中协调细胞皮层细胞骨架和质膜的组织。但其在单核细胞/巨噬细胞（MΦ）中的作用尚未完全了解。在这里，我们使用单核细胞/巨噬细胞特异性 ezrin 敲除小鼠模型来研究 ezrin 在单核细胞募集和对脂多糖（LPS）反应的肺细胞外基质（ECM）适应中的作用。我们的研究表明，LPS 诱导单核细胞/巨噬细胞中 ezrin 的表达，对于单核细胞黏附肺 ECM、增殖和分化为组织驻留的间质性 MΦs 是必需的。从机制上讲，单核细胞中 ezrin 的缺失会破坏黏着斑激酶和 AKT 丝氨酸-苏氨酸蛋白激酶信号的激活，这对于肺募集的单核细胞和单核细胞衍生的 MΦs 黏附 ECM、增殖和存活是必需的。总之，我们的数据表明，ezrin 除了具有结构细胞支持作用外，还在炎症过程中影响多种单核细胞/巨噬细胞过程和信号通路，促进其分化为组织驻留的巨噬细胞。
