**2.3 Apoptotic bodies**

*Extracellular Vesicles and Their Importance in Human Health*

accumulated within the multivesicular bodies, exocytosis [20]

tetraspanins, HSP70, HSP90, Alix, Rab5a/b

ceramide, noncoding RNA, mRNA, miRNA, and cytosol [31]

tolerosomes, dexosomes,

Prostasomes,

nanovesicles, exosome-like vesicles,

and others [18, 32]

*Classification of EVs based on size and their biogenesis.*

Organelles No No Yes

Biogenesis Endosomal pathway,

Marker proteins CD 9, CD63 and CD61,

Content Proteins, cholesterol,

[23–25]

Sedimentation

rate

Types of generation

Intracellular storage

Alternative names

Impact on the immune system

**Table 1.**

**Exosomes Ectosomes Apoptotic bodies**

100,000–120,000×g 16,000–20,000×g 5000–16,000×g

shedding [21]

Constitutive Regulated Regulated

Yes No No

Proteins, phosphatidylserine, cholesterol, mRNA, miRNA, and cytosol [31]

Nanoparticles, microparticles, microvesicles, shedding vesicles, shedding bodies, exovesicles, secretory vesicles, and oncosomes [18]

Immunostimulators Immunosuppressors Immunosuppressors

Generated directly from the plasma membrane by

TyA and C1a, ARF6 and VCAMP3, β1 integrins, selectins, CD40, MMP, lineage markers, and ezrin [26–28]

Cell fragmentation Blebbing or zeiosis bulge of membrane by increasing the surface area through tearing [22]

Calreticulin, TSP and C3b, and histones [29, 30].

phosphatidylserine, DNA, rRNA, and cytosol [18]

Apoptotic blebs [18]

Proteins,

Size 30–100 nm 100–1000 nm 500–4000 nm

Filtration 20–200 nm >200 nm >1000 nm

budding of the plasma membrane in specialized microdomains of the plasmalemma, the phenomenon known as microvesicle shedding [29]. They are released both by cells in normal resting state and by cells upon stimulation. Ectosome fusion with the plasma membrane of a recipient cell is followed by changes in antigens, enzymes, and other proteins in a specific site of plasmalemma, while their content release into the cytoplasm can alter the recipients' cell gene expression [64, 65]. Tumor-derived ectosomes were shown to have immunosuppressive properties by inducing the chemotaxis of granulocytes, lymphocytes, and monocytes due to several chemokines (e.g., particularly IL-8) transported in ectosomes [66].

Oncosomes are a particular type of ectosomes, excessively large, which can even reach 1000 nm, characteristic to advanced cancers. There is a confusion in the use of these terms in the literature and that is why we thought to treat oncosomes as a particular category of ectosomes. The generic name of ectosomes can include oncosomes, while the name of oncosomes excludes ectosomes released from normal cells. Oncosomes content is adapted to serve cancer metabolism, so they will contain enzymes involved in glucose, glutamine, and amino acid metabolism. Furthermore, oncosomes are enriched in proteins, which have a

**92**

Apoptotic bodies (ApoBDs) are the largest type of extracellular vesicles (typically 1–5μm in diameter) visible during an apoptotic process. Kerr in 1972 proposed the term "apoptotic body" [68]. ApoBDs are released as blebs of cells undergoing apoptosis and consist of cytoplasm, organelles with or without a nuclear fragment. It has also been shown that ApoBDs can harbor proteins, lipids, DNA, rRNA, organelles, and cytosol [18]; this is the reason why the disassembly of an apoptotic cell into ApoBDs can mediate intercellular communication and may contribute to the development of various disease states [69]. These bodies are then phagocytosed by macrophages or neoplastic cells and degraded within phagolysosomes. Their formation has been proposed to play an important role in the clearance of apoptotic cells by phagocytes. Different cell types can generate ApoBDs via different mechanisms [70]. These ApoBDs can be classified based on cell-type-specific surface markers and content. Jiang et al. showed that ApoBDs share the same surface markers as their cell of origin; this is the reason why apoptotic bodies are very different and can be divided into specific subclasses [70].

ApoBD occurs spontaneously in untreated malignant neoplasms, and is implicated in both physiological involution and atrophy of various tissues and organs. Pathological settings include inflammation [71], autoimmunity [72–74], viral infection [75], and tumorigenesis because they participate in the horizontal transfer of oncogenes due to their nuclear material content from the dying cells [76].
