Abstract:Production of extracellular vesicles (EVs) involved in intercellular communication is a common capacity of most cell types. Upon encountering opsonized microorganisms, neutrophilic granulocytes release EVs that compromise bacterial growth. We carried out a systematic investigation of the involvement of potential opsonin receptors in EV-generation from human and murine neutrophils. Applying flow cytometric, proteomic and functional analysis as well as using genetically modified mice, we demonstrate that formati… Show more
“…Integrin αvβ6-containing EVs released by prostate cancer cells mediate αvβ6 transfer to microvascular endothelial cells and promote endothelial cell motility and tube formation, in contrast to EVs isolated from β6 negative cancer cells [ 77 ]. Finally, integrins can regulate the sorting of fibronectin into cancer cell EVs, as well as the contents and antibacterial activity of neutrophil EVs, although how integrins crosstalk with the sorting machinery remains to be established [ 75 , 78 ]. Figure 4 Integrins Control Binding and Uptake of Extracellular Vesicles and Viruses.…”
Section: Integrins Control Uptake Of Extracellular Vesicles and Virusmentioning
Integrins are transmembrane receptors that transduce biochemical and mechanical signals across the plasma membrane and promote cell adhesion and migration. In addition, integrin adhesion complexes are functionally and structurally linked to components of the intracellular trafficking machinery and accumulating data now reveal that they are key regulators of endocytosis and exocytosis in a variety of cell types. Here, we highlight recent insights into integrin control of intracellular trafficking in processes such as degranulation, mechanotransduction, cell–cell communication, antibody production, virus entry, Toll-like receptor signaling, autophagy, and phagocytosis, as well as the release and uptake of extracellular vesicles. We discuss the underlying molecular mechanisms and the implications for a range of pathophysiological contexts, including hemostasis, immunity, tissue repair, cancer, and viral infection.
“…Integrin αvβ6-containing EVs released by prostate cancer cells mediate αvβ6 transfer to microvascular endothelial cells and promote endothelial cell motility and tube formation, in contrast to EVs isolated from β6 negative cancer cells [ 77 ]. Finally, integrins can regulate the sorting of fibronectin into cancer cell EVs, as well as the contents and antibacterial activity of neutrophil EVs, although how integrins crosstalk with the sorting machinery remains to be established [ 75 , 78 ]. Figure 4 Integrins Control Binding and Uptake of Extracellular Vesicles and Viruses.…”
Section: Integrins Control Uptake Of Extracellular Vesicles and Virusmentioning
Integrins are transmembrane receptors that transduce biochemical and mechanical signals across the plasma membrane and promote cell adhesion and migration. In addition, integrin adhesion complexes are functionally and structurally linked to components of the intracellular trafficking machinery and accumulating data now reveal that they are key regulators of endocytosis and exocytosis in a variety of cell types. Here, we highlight recent insights into integrin control of intracellular trafficking in processes such as degranulation, mechanotransduction, cell–cell communication, antibody production, virus entry, Toll-like receptor signaling, autophagy, and phagocytosis, as well as the release and uptake of extracellular vesicles. We discuss the underlying molecular mechanisms and the implications for a range of pathophysiological contexts, including hemostasis, immunity, tissue repair, cancer, and viral infection.
“…The radius of the particles was calculated using sphere approximation. 36 For nanoparticle tracking analysis (NTA), samples were resuspended in 1 ml of PBS to reach appropriate particle concentration range for the measurement. Particle size distribution and concentration were analyzed on ZetaView PMX120 instrument (Particle Metrix, Inning am Ammersee, Germany).…”
Section: Characterization Of the Size Distribution Of Pmn-derived Evsmentioning
confidence: 99%
“…EV-containing pellets were processed as described in our previous papers. 12,36 Briefly, pelleted EVs were fixed with 4% paraformaldehyde at room temperature for 1 h, rinsed by PBS, and post-fixed in 1% osmium tetroxide (OsO 4 )…”
Section: Transmission Electron Microscopic Investigation Of the Pmn-dmentioning
Extracellular vesicles (EVs) are important elements of intercellular communication. A plethora of different, occasionally even opposite, physiologic and pathologic effects have been attributed to these vesicles in the last decade. A direct comparison of individual observations is however hampered by the significant differences in the way of elicitation, collection, handling, and storage of the investigated vesicles. In the current work, we carried out a careful comparative study on 3, previously characterized types of EVs produced by neutrophilic granulocytes. We investigated in parallel the modulation of multiple blood-related cells and functions by medium-sized vesicles. We show that EVs released from resting neutrophils exert anti-inflammatory action by reducing production of reactive oxygen species (ROS) and cytokine release from neutrophils. In contrast, vesicles generated upon encounter of neutrophils with opsonized particles rather promote proinflammatory processes as they increase production of ROS and cytokine secretion from neutrophils and activate endothelial cells. EVs released from apoptosing cells were mainly active in promoting coagulation. We thus propose that EVs are "custom made," acquiring selective capacities depending on environmental factors prevailing at the time of their biogenesis.
“…Following MISEV 2018 guidelines, our group compared the characteristics of PMN-EV isolates prepared with DC and SEC (size exclusion chromatography). The SEC isolates showed similar physical and functional characteristics to the DC-prepared EV isolates, but the SEC-EV yield was significantly lower [ 140 ]. To avoid misinterpretation of results, careful quality control of the parent cells and the isolated EVs is needed.…”
Similar to other cell types, neutrophilic granulocytes also release extracellular vesicles (EVs), mainly medium-sized microvesicles/microparticles. According to published data, authors have reached a consensus on the physical parameters (size, density) and chemical composition (surface proteins, proteomics) of neutrophil-derived EVs. In contrast, there is large diversity and even controversy in the reported functional properties. Part of the discrepancy may be ascribed to differences in the viability of the starting cells, in eliciting factors, in separation techniques and in storage conditions. However, the most recent data from our laboratory prove that the same population of neutrophils is able to generate EVs with different functional properties, transmitting pro-inflammatory or anti-inflammatory effects on neighboring cells. Previously we have shown that Mac-1 integrin is a key factor that switches anti-inflammatory EV generation into pro-inflammatory and antibacterial EV production. This paper reviews current knowledge on the functional alterations initiated by neutrophil-derived EVs, listing their effects according to the triggering agents and target cells. We summarize the presence of neutrophil-derived EVs in pathological processes and their perspectives in diagnostics and therapy. Finally, the functional heterogeneity of differently triggered EVs indicates that neutrophils are capable of producing a broad spectrum of EVs, depending on the environmental conditions prevailing at the time of EV genesis.
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