Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Int J Mol Sci. 2021 Jul 25;22(15):7923. doi: 10.3390/ijms22157923.
Macrophages were first described as phagocytic immune cells responsible for maintaining tissue homeostasis by the removal of pathogens that disturb normal function. Historically, macrophages have been viewed as terminally differentiated monocyte-derived cells that originated through hematopoiesis and infiltrated multiple tissues in the presence of inflammation or during turnover in normal homeostasis. However, improved cell detection and fate-mapping strategies have elucidated the various lineages of tissue-resident macrophages, which can derive from embryonic origins independent of hematopoiesis and monocyte infiltration. The role of resident macrophages in organs such as the skin, liver, and the lungs have been well characterized, revealing functions well beyond a pure phagocytic and immunological role. In the heart, recent research has begun to decipher the functional roles of various tissue-resident macrophage populations through fate mapping and genetic depletion studies. Several of these studies have elucidated the novel and unexpected roles of cardiac-resident macrophages in homeostasis, including maintaining mitochondrial function, facilitating cardiac conduction, coronary development, and lymphangiogenesis, among others. Additionally, following cardiac injury, cardiac-resident macrophages adopt diverse functions such as the clearance of necrotic and apoptotic cells and debris, a reduction in the inflammatory monocyte infiltration, promotion of angiogenesis, amelioration of inflammation, and hypertrophy in the remaining myocardium, overall limiting damage extension. The present review discusses the origin, development, characterization, and function of cardiac macrophages in homeostasis, cardiac regeneration, and after cardiac injury or stress.
巨噬细胞最初被描述为吞噬免疫细胞，通过清除干扰正常功能的病原体来维持组织内稳态。从历史上看，巨噬细胞被视为终末分化的单核细胞来源的细胞，起源于造血，并在炎症存在或正常稳态下细胞更替时浸润到多个组织中。然而，改进的细胞检测和谱系追踪策略阐明了组织驻留巨噬细胞的各种谱系，它们可以独立于造血和单核细胞浸润从胚胎起源中衍生而来。驻留巨噬细胞在皮肤、肝脏和肺部等器官中的作用已经得到很好的描述，揭示了除了吞噬和免疫作用之外的多种功能。在心脏中，通过谱系追踪和基因耗竭研究，最近的研究开始揭示各种组织驻留巨噬细胞群体的功能作用。其中一些研究阐明了心脏驻留巨噬细胞在维持心脏内稳态中的新的、意想不到的作用，包括维持线粒体功能、促进心脏传导、冠状动脉发育和淋巴管生成等。此外，在心脏损伤后，心脏驻留巨噬细胞表现出多种功能，如清除坏死和凋亡细胞及碎片、减少炎症性单核细胞浸润、促进血管生成、减轻炎症和改善剩余心肌的肥大，从而总体限制损伤的扩展。本综述讨论了心脏巨噬细胞在心脏内稳态、心脏再生以及心脏损伤或应激后的起源、发育、特征和功能。
