Читать книгу Genomic and Epigenomic Biomarkers of Toxicology and Disease - Группа авторов - Страница 35

Various particles are secreted by cells and released into body fluids such as blood, urine, ascites, amniotic fluid, bronchoalveolar lavage, and tears; the International Society for Extracellular Vesicles (ISEV) has named these particles “extracellular vesicles” (EVs) (Thery et al. 2002; Witwer et al. 2017). EVs are divided into three subtypes: exosomes, microvesicles (MVs), and apoptotic bodies. This classification is based on their size and on the biosynthetic pathways by which they are generated (see Figure 3.1 and Table 3.1; also Colombo et al. 2014).

Figure 3.1 Schematic illustration of extracellular vesicles (EVs). EVs include exosomes, microvesicles and apoptotic bodies. MVB: multivesicular body.

Exosomes are thought to derive from intraluminal vesicles through the fusion of an intermediate endocytic compartment, the multivesicular body (MVB), with the plasma membrane (Witwer et al. 2013; Cufaro et al. 2019). The MVB contains vesicles that bind either to lysosomes, to degrade their contents, or to the plasma membrane. The latter produces the release of intraluminal vesicles defined as exosomes into extracellular space (Harding and Stahl 1983; Pan et al. 1985).

As already mentioned, exosomes are approximately 100 nm in diameter; hence they are smaller than MVs (Witwer et al. 2013). Exosome membrane proteins are enriched in heat shock proteins (HSP70, HSP90), integrins (LFA-1), proteins involved in MVB formation (ALIX, TSG101), tetraspanins (CD9, CD63, CD81, CD82, and CD151), immunostimulatory molecules (MHC class I/II proteins), lipid-related proteins, and phospholipases (Conde-vancells et al. 2008; Subra et al. 2010).

Table 3.3 Main characteristics of exosomes, microvesicles (MV), and apoptotic bodies.

	Exosomes	Microvesicles	Apoptotic Bodies
Origin	Endocytic pathway	Plasma membrane	Plasma membrane
Size	40–120 nm	50–1000 nm	500–2000 nm
Function	Intercellular communication	Intercellular communication	Facilitate phagocytosis
Markers	Alix, Tsg101, tetraspanins	Selectins, integrins, CD proteins, DNA, RNA40 ligand	Histones, annexin V
Contents	Protein, DNA, RNA	Protein, DNA, RNA	Nuclear fractions, cell organelles

By contrast, MVs range from a few nanometers to a few microns in diameter and derive from outward budding of the plasma membrane (Witwer et al. 2013; Kalluri 2016). In some lipids and phosphatidylserine they are enriched.

Apoptotic bodies are released by apoptotic cells. They are the largest EVs, with a diameter of 1 to 5 μm, and contain several intracellular fragments, cellular organelles, membranes, and cytosolic contents (van der Pol et al. 2012; Cufaro et al. 2019). However, in practice it remains difficult to distinguish between the different subtypes of EVs. Therefore the ISEV recommends, by consensus, using the general term “EV” in the nomenclature (Gould and Raposo 2013; Thery et al. 2018). In this chapter we use this term to refer to all the subtypes of vesicles present in the extracellular space, alongside small EVs (sEVs) for exosomes.

Additional components are found in EVs, including a wide variety of genetic molecules such as DNA and coding or non-coding RNAs (Nawaz et al. 2018).