Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses

Acta Pharm Sin B. 2021 Jun;11(6):1493-1512. doi: 10.1016/j.apsb.2020.12.014. Epub 2020 Dec 19.


Macrophages are typically identified as classically activated (M1) macrophages and alternatively activated (M2) macrophages, which respectively exhibit pro- and anti-inflammatory phenotypes, and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation, injury, and repair processes. Recent studies indicate that tissue cells and macrophages interact via the release of small extracellular vesicles (EVs) in processes where EVs released by stressed tissue cells can promote the activation and polarization of adjacent macrophages which can in turn release EVs and factors that can promote cell stress and tissue inflammation and injury, and vice versa. This review discusses the roles of such EVs in regulating such interactions to influence tissue inflammation and injury in a number of acute and chronic inflammatory disease conditions, and the potential applications, advantage and concerns for using EV-based therapeutic approaches to treat such conditions, including their potential role of drug carriers for the treatment of infectious diseases.

Keywords: ADSCs, adipose-derived stem cells; AKI, acute kidney injury; ALI, acute lung injury; AMs, alveolar macrophages; BMSCs, bone marrow stromal cells; CLP, cecal ligation and puncture; DSS, dextran sodium sulphate; EVs, extracellular vesicles; Extracellular vesicles; HSPA12B, heat shock protein A12B; HUCMSCs, human umbilical cord mesenchymal stem cells; IBD, inflammatory bowel disease; ICAM-1, intercellular adhesion molecule 1; IL-1β, interleukin-1β; Inflammatory disease; Interaction loop; KCs, Kupffer cells; KLF4, krüppel-like factor 4; LPS, lipopolysaccharides; MHC, major histocompatibility complex; MSCs, mesenchymal stromal cells; MVs, microvesicles; Macrophage; PEG, polyethylene glycol; PMFA, 5,7,30,40,50-pentamethoxyflavanone; PPARγ, peroxisome proliferator-activated receptor γ; SIRPα, signal regulatory protein α; Sepsis; Stem cell; TECs, tubular epithelial cells; TNF, tumor necrosis factor; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; Targeted therapy; Tissue injury; iNOS, inducible nitrogen oxide synthase.

Publication types

  • Review