Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

Abstract

Two types of extracellular vesicles (EVs), exosomes and ectosomes, are generated and released by all cells, including immune cells. The two EVs appear different in many properties: size, mechanism and site of assembly, composition of their membranes and luminal cargoes, sites and processes of release. In functional terms, however, these differences are minor. Moreover, their binding to and effects on target cells appear similar, thus the two types are considered distinct only in a few cases, otherwise they are presented together as EVs. The EV physiology of the various immune cells differs as expected from their differential properties. Some properties, however, are common: EV release, taking place already at rest, is greatly increased upon cell stimulation; extracellular navigation occurs adjacent and at distance from the releasing cells; binding to and uptake by target cells are specific. EVs received from other immune or distinct cells govern many functions in target cells. Immune diseases in which EVs play multiple, often opposite (aggression and protection) effects, are numerous; inflammatory diseases; pathologies of various tissues; and brain diseases, such as multiple sclerosis. EVs also have effects on interactive immune and cancer cells. These effects are often distinct, promoting cytotoxicity or proliferation, the latter together with metastasis and angiogenesis. Diagnoses depend on the identification of EV biomarkers; therapies on various mechanisms such as (1) removal of aggression-inducing EVs; (2) EV manipulations specific for single targets, with insertion of surface peptides or luminal miRNAs; and (3) removal or re-expression of molecules from target cells.

Measuring Extracellular Vesicles by Conventional Flow Cytometry: Dream or Reality?

“…They diverge into two main subgroups according to their biogenesis and release mechanism: microvesicles (150–1000 nm in diameter, MVs) shed from the plasma membrane, and exosomes, which are generally smaller in size (30–150 nm in diameter, EXOs) originating from the endosome as intraluminal vesicles enclosed within multivesicular bodies [ 1 ]. EVs are central in regulating multiple physiological processes—e.g., tissue repair, stem cell maintenance and coagulation―and pathophysiological processes―e.g., cancer, neurodegenerative diseases and viral infections [ 2 ]—because of their ability to transfer biological content. Since EVs are found in accessible body fluids and express a variety of bioactive molecules of the cells of origin, intense research is being conducted to understand EVs’ potential as biomarkers for personalized medicine, and to develop relatively simple and fast methods to assess EVs in translational studies using high-throughput technologies.…”

The Potential Role of Extracellular Vesicles in COVID-19 Associated Endothelial injury and Pro-inflammation

“…Extracellular vesicles (EVs) carry coding and non-coding RNA, proteins, DNA fragments, and lipids, which facilitate crosstalk between cells. This transfer of EV cargo plays a significant role in a number of diseases processes, including cardiovascular disease, pulmonary hypertension, and various malignancies ( 5 , 6 ). EVs can be released in response to thrombin, shear stress, complement activation, and inflammation, among other pathophysiologic triggers.…”

Platelets Extracellular Vesicles as Regulators of Cancer Progression—An Updated Perspective

“…Lipid bilayer membrane protects their cargo from enzymes like proteases and ribonucleases [ 6 ]. The largest of EVs are ABs (with diameter 1–5 µm) represented by clumps of material generated during the late stage of cell apoptosis [ 5 , 6 , 7 ].…”

“…During activation, maturation, proliferation, stress, aging, or apoptosis, cells shed EVs into the extracellular space [ 8 ]. Their presence in a number of body fluids including—urine, synovial fluid, bronchoalveolar lavage fluid, saliva, and bile was confirmed [ 7 , 9 , 10 , 11 ]. In the bloodstream, EVs are released by—erythrocytes, leukocytes, platelets (PEVs), megakaryocytes, and endothelial cells [ 10 , 12 ].…”