Abstract
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.
Highlights
Ccl2), is the main inflammation [35,36,37,38,39]. Classification using these markers is useful since chemokine receptor 2 (Ccr2)− macrochemokine that mediates monocyte infiltration to multiple tissues during acute and perphages are derived from yolk-sac precursors independent of monocytes, while most Ccr2+
These Ccr2+ macrophages are derived from monocytes which originate in the bone marrow or extramedullary tissues and show 50% replenishment by circulating monocytes within 3 weeks [10], depending on the Ccl2-Ccr2 signaling to infiltrate the heart [10,41,42]
Most macrophages with reparative and fibrotic phenotypes seem to be derived from the initial Ccr2+ Cx3cr1lo Ly6chi monocyte infiltration [76], as opposed to developing from the “patrolling” Ccr2− Cx3cr1hi Ly6clo monocyte infiltration, which is described as anti-inflammatory and as mediating homeostatic functions, reviewed in [87,88]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. New research tools that look at macrophages at the transcriptomic or proteomic level, have unveiled the heterogeneity of these tissue-resident cells, describing how they exist as clusters of subpopulations with distinct and overlapping functions [9,10,11,12,13]. These cells perform constant surveillance and phagocytosis of foreign and deleterious cells and material that may alter the normal function of their microenvironment [8,14,15,16,17,18,19,20,21,22]. We present a detailed review of the literature describing the ontogeny, development, characterization, and role of cardiac-resident macrophages in both homeostasis and after injury
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
