Abstract
Macrophages are effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators. In addition, macrophages play an important role in eliminating diseased and damaged cells through their programmed cell death. Generally, macrophages ingest and degrade dead cells, debris, tumor cells, and foreign materials. They promote homeostasis by responding to internal and external changes within the body, not only as phagocytes, but also through trophic, regulatory, and repair functions. Recent studies demonstrated that macrophages differentiate from hematopoietic stem cell-derived monocytes and embryonic yolk sac macrophages. The latter mainly give rise to tissue macrophages. Macrophages exist in all vertebrate tissues and have dual functions in host protection and tissue injury, which are maintained at a fine balance. Tissue macrophages have heterogeneous phenotypes in different tissue environments. In this review, we focused on the phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis for a better understanding of the role of tissue macrophages in several pathological conditions.
Highlights
Macrophages have a defensive function against pathogens such as microbes, and play an important role in the homeostatic maintenance of the body through the disposal of internal waste materials and tissue repair
Tissue macrophages in the spleen can be distinguished as (1) red pulp macrophages, (2) marginal zone metallophilic macrophages distributed inside the marginal zone, (3) marginal zone macrophages distributed outside the marginal zone, and (4) tingible body macrophages distributed in the lymph follicle of the white pulp region [71,72]
A drastic enhancement of vascular density promotes the oxygenation of and nutrient supply to tumor cells. Vascularization inducers such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), tumor necrosis factor (TNF)-α, basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), thymidine phosphorylase, CXCL8, and CCL2 are produced in Tumor-associated macrophages (TAMs) [94,95], and there are many reports indicating an association between the density of M2-TAMs and blood vessel density [92]
Summary
Macrophages have a defensive function against pathogens such as microbes, and play an important role in the homeostatic maintenance of the body through the disposal of internal waste materials and tissue repair. As macrophages have the ability to present antigens to T cells and function as effectors for cell-mediated immunity, it is known that they affect the development of infectious diseases, cancers, and chronic inflammatory diseases such as arteriosclerosis. Phagocytosis plays a critical role in that process. Macrophages exist in all vertebrate tissues, and different stimuli will affect macrophage phenotypes differently. It is known that the M1 and M2 nomenclature is too simplistic to describe the many distinct polarization phenotypes that are seen in tissue macrophages and are driven by many different environmental stimuli including cytokines, fatty acids, prostaglandins, and pathogen-derived molecules such as lipopolysaccharides (LPSs). We focused on the functions of macrophages in several pathological conditions from the point of view of phagocytosis
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