Macrophage-Derived Small Extracellular Vesicles in Multiple Diseases: Biogenesis, Function, and Therapeutic Applications

Abstract

Macrophages (Mφs), as immune cells, play a pivotal role against pathogens and many diseases, such as cancer, inflammation, cardiovascular diseases, orthopedic diseases, and metabolic disorders. In recent years, an increasing number of studies have shown that small extracellular vesicles (sEVs) derived from Mφs (M-sEVs) play important roles in these diseases, suggesting that Mφs carry out their physiological functions through sEVs. This paper reviews the mechanisms underlying M-sEVs production via different forms of polarization and their biological functions in multiple diseases. In addition, the prospects of M-sEVs in disease diagnosis and treatment are described.

Dendrocandin U from Dendrobium officinale Kimura et Migo Inhibits M1 Polarization in Alveolar Macrophage by Suppressing NF‐κB Signaling Pathway

“…In addition, M1 is inflammatory, usually induced by IFN-γ, TNF-α or LPS and expresses specific markers, such as iNOS, CD86, CD16/32, TNF-α, IL-6 and so on. [43] iNOS is not only a key enzyme to induce NO secretion, but also an important downstream factor of NF-kB signaling pathway, which can respond to inflammatory stimulation. [44] TNF-α plays an indispensable role in regulating immune cells and inflammatory responses, and TNF-α dysregulation can cause inflammatory responses such as fever, edema and tissue damage.…”

“…Phalloidin staining showed that dendrocandin U could significantly improve the inflammatory morphological changes of macrophages (Figure 4), which was related to the inhibition of their transformation to M1 phenotype. In addition, M1 is inflammatory, usually induced by IFN‐γ, TNF‐α or LPS and expresses specific markers, such as iNOS, CD86, CD16/32, TNF‐α, IL‐6 and so on [43] . iNOS is not only a key enzyme to induce NO secretion, but also an important downstream factor of NF‐κB signaling pathway, which can respond to inflammatory stimulation [44] .…”

Osteoimmune Interactions and Therapeutic Potential of Macrophage-Derived Small Extracellular Vesicles in Bone-Related Diseases

“…8 sEVs, with a diameter of 30-200 nm, are released by different cells, originate from the endocytic pathway 7 and widely distributed in a variety of body fluids. 9,10 All cells can release sEVs regardless of whether they are in a state of normal or pathological conditions. Due to their different sizes, levels, contents and origins, sEVs have great heterogeneity and target specific organs or cells, leading to different biological functions.…”

Regulation of Extracellular Vesicle-Mediated Immune Responses against Antigen-Specific Presentation

“…EVs are produced by various immune cells, including B and T cells, macrophages, dendritic cells (DC), natural killer (NK) cells, mast cells, and thymocytes [ 164 , 214 , 215 , 216 , 217 , 218 ] and are rich in proteins with immune functions, such as antigen-presenting molecules (major histocompatibility complex (MHC) class I, MHC class II, CD1), adhesion molecules (CD11b, intercellular adhesion molecule 1 (ICAM-1)), and co-stimulatory proteins (CD86) [ 219 , 220 , 221 , 222 ]. Additionally, exosomes are involved in releasing intracellular components to the outside of cells as waste products, and through their loaded immune-related molecules, they have various immune functions, such as antigen presentation, including the priming of early T cells, differentiation of mature T cells, development of effector functions, and regulation of immune-related cells [ 223 , 224 , 225 , 226 , 227 ].…”