Microvesicles (ectosomes, or microparticles) are a type of extracellular vesicle (EV) that are released from the cell membrane. In multicellular organisms, microvesicles and other EVs are found both in tissues (in the interstitial space between cells) and in many types of body fluids. Delimited by a phospholipid bilayer, microvesicles can be as small as the smallest EVs (30 nm in diameter) or as large as 1000 nm. They are considered to be larger, on average, than intracellularly-generated EVs known as exosomes. Microvesicles play a role in intercellular communication and can transport molecules such as mRNA, miRNA, and proteins between cells.
Though initially dismissed as cellular debris, microvesicles may reflect the antigenic content of the cell of origin and have a role in cell signaling. Like other EVs, they have been implicated in numerous physiologic processes, including anti-tumor effects, tumor immune suppression, metastasis, tumor-stroma interactions, angiogenesis, and tissue regeneration. Microvesicles may also remove misfolded proteins, cytotoxic agents and metabolic waste from the cell. Changes in microvesicle levels may indicate diseases including cancer.
Formation and contents
Different cells can release microvesicles from the plasma membrane. Sources of microvesicles include megakaryocytes, blood platelets, monocytes, neutrophils, tumor cells and placenta.
Platelets play an important role in maintaining hemostasis: they promote thrombus growth, and thus they prevent loss of blood. Moreover, they enhance immune response, since they express the molecule CD154 (CD40L). Platelets are activated by inflammation, infection, or injury, and after their activation microvesicles containing CD154 are released from platelets. CD154 is a crucial molecule in the development of T cell-dependent humoral immune response. CD154 knockout mice are incapable of producing IgG, IgE, or IgA as a response to antigens. Microvesicles can also transfer prions and molecules CD41 and CXCR4.
Endothelial microparticles
Endothelial microparticles are small vesicles that are released from endothelial cells and can be found circulating in the blood.
The microparticle consists of a plasma membrane surrounding a small amount of cytosol. The membrane of the endothelial microparticle contains receptors and other cell surface molecules which enable the identification of the endothelial origin of the microparticle, and allow it to be distinguished from microparticles from other cells, such as platelets.
Although circulating endothelial microparticles can be found in the blood of normal individuals, increased numbers of circulating endothelial microparticles have been identified in individuals with certain diseases, including hypertension and cardiovascular disorders, and pre-eclampsia and various forms of vasculitis. The endothelial microparticles in some of these disease states have been shown to have arrays of cell surface molecules reflecting a state of endothelial dysfunction. Therefore, endothelial microparticles may be useful as an indicator or index of the functional state of the endothelium in disease, and may potentially play key roles in the pathogenesis of certain diseases, including rheumatoid arthritis.
Endothelial microparticles have been found to prevent apoptosis in recipient cells by inhibiting the p38 pathway via inactivating mitogen-activated protein kinase (MKP)-1. Uptake of endothelial micoparticles is Annexin I/Phosphatidylserine receptor dependant.
Microparticles are derived from many other cell types.
Process of formation
Microvesicles and exosomes are formed and released by two slightly different mechanisms. These processes result in the release of intercellular signaling vesicles. Microvesicles are small, plasma membrane-derived particles that are released into the extracellular environment by the outward budding and fission of the plasma membrane. This budding process involves multiple signaling pathways including the elevation of intracellular calcium and reorganization of the cell's structural scaffolding. The formation and release of microvesicles involve contractile machinery that draws opposing membranes together before pinching off the membrane connection and launching the vesicle into the extracellular space.
Microvesicle budding takes place at unique locations on the cell membrane that are enriched with specific lipids and proteins reflecting their cellular origin. At these locations, proteins, lipids, and nucleic acids are selectively incorporated into microvesicles and released into the surrounding environment.