Extracellular Vesicles (EV)

Extracellular vesicles (EVs) are small membrane-bound vesicles released by most eukaryotic cells. They are present in various human and animal body fluids. The discovery of EVs dates back to the work of Pan and Johnstone, who identified them during platelet differentiation (1). Initially, EVs were thought to function primarily in cellular waste removal. However, subsequent research revealed that they contain major histocompatibility complex (MHC) molecules, indicating a potential role in antigen presentation (2, 3, 4).

Meaning and purpose

Extracellular vesicles (EVs) are tiny, lipid-bound carriers. They are released by many eukaryotic cells (5)

Cell-released vesicles with membranous structures, collectively referred to as EVs are widely reported to be involved in cell-cell communication by their secretion and uptake (9).

Bacterial extracellular vesicles (EVs) are another weapon gut bacteria use to induce intestinal and extra-intestinal effects. Depending on which bacteria the EVs originate from, they promote pro- (EVs from pathogenic bacteria) or anti-inflammatory (EVS from commensal bacteria) responses (10).

Extraintestinally, EVs may prime neutrophils for inflammatory responses elicited by secondary stimuli (11)

Coming from..

Extracellular vesicles (EV) are membrane vesicles that are released from numerous cell types, including intestinal epithelial cells (exosomes) and bacteria (outer membrane vesicles (OMV), membrane vesicles) (12, 13, 14).

Contents

EVs carry specific cargos from infected cells. This makes them useful as biomarkers for diseases. Viruses can use the EV machinery to spread. EVs from infected cells can carry immune molecules. This helps in disease progression (5).

EV contain toxins, nucleic acids, proteins (including cytokines), and genetic material and are capable of crossing the BBB and influencing neuroinflammation and brain function (15).

Extracellular vesicles released by APCs carry surface MHC class I and class II molecules (16)

Classification

EVs are classified into three main types based on their size, content, and origin (5):

• Apoptotic Bodies:
  
  
  • Size: 500 to 2,000 nm
  
  
  • Origin: Formed from cell blebbing during apoptosis
  
  
  
  


• Microvesicles:
  
  
  • Size: 100 to 1,000 nm
  
  
  • Origin: Bud from the plasma membrane of healthy cells
  
  
  • Function: Contribute to maintaining cellular homeostasis
  
  
  
  


• Exosomes:
  
  
  • Size: 30 to 150 nm
  
  
  • Origin: Originate from the endosomal system, which includes early, late, and recycling endosomes
  
  
  
  

Microvesicles, ectosomes, oncosomes, apoptotic bodies, exosomes (17).

Formation and Sorting Mechanisms

The formation of exosomes involves the invagination of the plasma membrane to create endosomes. Early endosomes develop into intraluminal vesicles (ILVs), which then fuse to form multivesicular bodies (MVBs). During this process, proteins, nucleic acids, and lipids are sorted, often utilizing the endosomal sorting complexes required for transport (ESCRT) (6). Interestingly, EVs can form with or without the involvement of ESCRT (7, 8), though the specific conditions that favor one pathway over the other remain unclear. MVBs typically contain ILVs ranging from 30 to 100 nm in size (18).

References

(1) Pan & Johnstone 1983 Cell 33: 967-978
(2) Johnstone et al. 1987 J Biol Chem 262: 9412-9420
(3) Yuana et al. 2013 Blood Rev 27: 31-39
(4) György et al. 2011 Cell Mol Life Sci 68: 2667-2688
(5) Kumari & Banerjee 2026 mBio 17: e03316-25
(6) Harding et al. 1983 J Cell Biol 97: 329-339
(7) Babst et al. 2002 Dev Cell 3: 283-289
(8) Katzmann et al. 2001 Cell 106: 145-155
(9) Théry et al. 2018 J Extracell Vesicles 7: 1535750
(10) Macia et al. 2019 Int J Mol Sci 21: 107
(11) Lajqi et al. 2022 Biomedicines 10: 442
(12) András & Toborek 2016 Tissue Barriers 4: e1131804
(13) Van Niel et al. 2018 Nat Rev Mol Cell Biol 19: 213-228
(14) Doyle & Wang 2019 Cells 8: 727
(15) Cuesta et al. 2021 Int J Mol Sci 22: 4235
(16) Robbins & Morelli 2014
(17) Tetta et al. 2013 Endocrine 44: 11-19
(18) Zhou et al. 2021 EBioMedicine 67: 103365

see also:
Blood Brain Barrier (BBB)