Abstract
Microvesicles (MVs) are released from almost all cell brain types into the microenvironment and are emerging as a novel way of cell-to-cell communication. This review focuses on MVs discharged by microglial cells, the brain resident myeloid cells, which comprise ∼10–12% of brain population. We summarize first evidence indicating that MV shedding is a process activated by the ATP receptor P2X7 and that shed MVs represent a secretory pathway for the inflammatory cytokine IL-β. We then discuss subsequent findings which clarify how IL-1 β can be locally processed and released from MVs into the extracellular environment. In addition, we describe the current understanding about the mechanism of P2X7-dependent MV formation and membrane abscission, which, by involving sphingomyelinase activity and ceramide formation, may share similarities with exosome biogenesis. Finally we report our recent results which show that microglia-derived MVs can stimulate neuronal activity and participate to the propagation of inflammatory signals, and suggest new areas for future investigation.
Highlights
SUBCELLULAR ORIGIN AND COMPOSITION OF MVs SHED FROM THE CELL SURFACE Microvesicles (MVs), referred to as shed vesicles or ectosomes (Sadallah et al, 2011), are small (0.1–1 μm) vesicles which bud directly from the plasma membrane and are released into the extracellular environment upon cell activation
This mechanism includes the bud of intraluminal vesicles at endosomes during multivesicular bodies (MVBs) maturation and subsequent vesicle secretion upon fusion of multi vesicular bodies (MVBs) with the plasma membrane
A few years ago we reported that a MV-mediated mechanism for IL-1β release occurs in microglial cells (Bianco et al, 2005), very similar to that first described in monocytes (MacKenzie et al, 2001)
Summary
EMERGING ROLE OF MVs DERIVED FROM BRAIN CELLS: P2X7-DEPENDENT MV SHEDDING AND IL-1β RELEASE IN MICROGLIA In the recent years, a series of studies has indicated relevant physiological and pathological functions for extracellular vesicles within the brain These functions include fundamental processes occurring in brain, such as axonal growth and regeneration, axon-glia communication, inter-neuronal transfer of information across synapses, modulation of neuro-immune interactions, as well as disease-associated events, including tumor progression, and spreading of pathogenic agents or misfolded proteins. The majority of these studies focused, on exosomes rather than MVs shed from the cell surface of brain cells (Table 1). We found that shedding of MVs from microglial cells is promoted
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