Sabe Hideaki, Yahara Yasuhito, Ishii Masaru
Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Suita, Osaka, 565-0871, Japan.
WPI-Immunology Frontier Research Center, Osaka University, Suita, Osaka, 565-0871, Japan.
Inflamm Regen. 2024 Nov 27;44(1):49. doi: 10.1186/s41232-024-00360-3.
Cell-cell fusion is a vital biological process where the membranes of two or more cells merge to form a syncytium. This phenomenon is critical in various physiological and pathological contexts, including embryonic development, tissue repair, immune responses, and the progression of several diseases. Osteoclasts, which are cells from the monocyte/macrophage lineage responsible for bone resorption, have enhanced functionality due to cell fusion. Additionally, other multinucleated giant cells (MGCs) also arise from the fusion of monocytes and macrophages, typically during chronic inflammation and reactions to foreign materials such as prostheses or medical devices. Foreign body giant cells (FBGCs) and Langhans giant cells (LGCs) emerge only under pathological conditions and are involved in phagocytosis, antigen presentation, and the secretion of inflammatory mediators. This review provides a comprehensive overview of the mechanisms underlying the formation of multinucleated cells, with a particular emphasis on macrophages and osteoclasts. Elucidating the intracellular structures, signaling cascades, and fusion-mediating proteins involved in cell-cell fusion enhances our understanding of this fundamental biological process and helps identify potential therapeutic targets for disorders mediated by cell fusion.
细胞-细胞融合是一个至关重要的生物学过程，在此过程中，两个或更多细胞的膜融合形成一个多核体。这种现象在各种生理和病理情况下都至关重要，包括胚胎发育、组织修复、免疫反应以及多种疾病的进展。破骨细胞来自单核细胞/巨噬细胞谱系，负责骨吸收，由于细胞融合，其功能得到增强。此外，其他多核巨细胞（MGCs）也源自单核细胞和巨噬细胞的融合，通常发生在慢性炎症以及对诸如假体或医疗器械等异物的反应过程中。异物巨细胞（FBGCs）和朗汉斯巨细胞（LGCs）仅在病理条件下出现，并参与吞噬作用、抗原呈递和炎症介质的分泌。本综述全面概述了多核细胞形成的潜在机制，特别着重于巨噬细胞和破骨细胞。阐明细胞-细胞融合过程中涉及的细胞内结构、信号级联反应和融合介导蛋白，有助于我们加深对这一基本生物学过程的理解，并有助于确定由细胞融合介导的疾病的潜在治疗靶点。
