Actin and Actin-Associated Proteins in Extracellular Vesicles Shed by Osteoclasts

Holliday, L. Shannon; Faria, Lorraine Perciliano de; Rody, Wellington J.

doi:10.3390/ijms21010158

Cited by 32 publications

(32 citation statements)

References 119 publications

(148 reference statements)

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“…Among the altered processes in C5a-treated neutrophils, we found MV- relevant processes, such as catabolic and metabolic processes of glycosyl- and glyco-lipids, phospholipids and ceramids as well as activation and regulation of small GTPases ( Supplemental Table 1 ). Further MV-relevant changes in pathways involve cytoskeleton-based processes ( 31 ), cell shape changes, and MAPK activity ( 32 ) ( Supplemental Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Complement C5a Induces Pro-inflammatory Microvesicle Shedding in Severely Injured Patients

et al. 2020

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Initially underestimated as platelet dust, extracellular vesicles are continuously gaining interest in the field of inflammation. Various studies addressing inflammatory diseases have shown that microvesicles (MVs) originating from different cell types are systemic transport vehicles carrying distinct cargoes to modulate immune responses. In this study, we focused on the clinical setting of multiple trauma, which is characterized by activation and dysfunction of both, the fluid-phase and the cellular component of innate immunity. Given the sensitivity of neutrophils for the complement anaphylatoxin C5a, we hypothesized that increased C5a production induces alterations in MV shedding of neutrophils resulting in neutrophil dysfunction that fuels posttraumatic inflammation. In a mono-centered prospective clinical study with polytraumatized patients, we found significantly increased granulocyte-derived MVs containing the C5a receptor (C5aR1, CD88) on their surface. This finding was accompanied by a concomitant loss of C5aR1 on granulocytes indicative of an impaired cellular chemotactic and pro-inflammatory neutrophil functions. Furthermore, in vitro exposure of human neutrophils (from healthy volunteers) to C5a significantly increased MV shedding and C5aR1 loss on neutrophils, which could be blocked using the C5aR1 antagonist PMX53. Mechanistic analyses revealed that the interaction between C5aR1 signaling and the small GTPase Arf6 acts as a molecular switch for MV shedding. When neutrophil derived, C5a-induced MV were exposed to a complex ex vivo whole blood model significant pro-inflammatory properties (NADPH activity, ROS and MPO generation) of the MVs became evident. C5a-induced MVs activated resting neutrophils and significantly induced IL-6 secretion. These data suggest a novel role of the C5a-C5aR1 axis: C5a-induced MV shedding from neutrophils results in decreased C5aR1 surface expression on the one hand, on the other hand it leads to profound inflammatory signals which likely are both key drivers of the neutrophil dysfunction which is regularly observed in patients suffering from multiple traumatic injuries.

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Section: Resultsmentioning

confidence: 99%

Complement C5a Induces Pro-inflammatory Microvesicle Shedding in Severely Injured Patients

et al. 2020

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“…For cytoskeletal proteins, we cannot exclude that these proteins are all cellular contaminants, in spite of the thorough cleaning of the skeletal tissues by sodium hypochlorite. We cannot rule out neither that a tight link exists between these proteins and the extracellular matrix, several evidences show it, in particular when vesicles are involved in the process: actin was found to be a component of ECM (Accinni et al, 1983); in cartilage, it is associated to ECM in mineralizing/demineralizing vesicles (Holliday et al, 2020;Rosenthal et al, 2011). In molluscs,…”

Section: Discussionmentioning

confidence: 97%

The shell matrix and microstructure of the Ram’s Horn squid: Molecular and structural characterization

Oudot

Neige

Shir

et al. 2020

Journal of Structural Biology

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Molluscs are one of the most diversified phyla among metazoans. Most of them produce an external calcified shell, resulting from the secretory activity of a specialized epithelium of the calcifying mantle. This biomineralization process is controlled by a set of extracellular macromolecules, collectively defined as the organic matrix. In spite of several studies, these components are mainly known for bivalve and gastropod classes. In the present study, we investigated the physical and biochemical properties of the internal planispiral shell of the understudied Ram's Horn squid Spirula spirula (Cephalopoda, Decabrachia, Spirulida). Scanning Electron Microscope investigations of the shell reveal a complex microstructural organization, with septa sandwiched into the shell wall, in the form of a bevel. The saccharides constitute a quantitatively important moiety of the matrix, as shown by Fourier-transform infrared spectroscopy. Solid-state nuclear magnetic resonance spectroscopy identified β-chitin and additional polysaccharides, for a total amount of 80% of the insoluble fraction. Proteomics was applied to both soluble and insoluble matrices and in silico searches were performed, first on heterologous metazoans models, and secondly, on an unpublished transcriptome of Spirula spirula. In the first case, several peptides were identified, some of them matching with tyrosinase, chitinase 2, protease inhibitor, or immunoglobulin. In the second case, 38 hits were obtained, including transferrin, a serine protease inhibitor, matrilin, different histone-like, a 2-macroglobulin or a putative heme-binding/calcium-binding protein. The very few similarities with known molluscan shell matrix proteins suggest that Spirula spirula uses a unique set of shell matrix proteins for constructing its internal shell. The absence of similarity with closely related cephalopods such as the cuttlefish Sepia demonstrates that there is no obvious phylogenetic signal in the skeletal matrix of cephalopods.

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“…Components of future microvesicles are locally accumulated on the inner membrane side, then the membrane curves, forming a vesicle. This process is accompanied by specific translocase-mediated transfer of phosphatidylserine to the outer plasma membrane layer and contraction of the submembrane actin cytoskeleton [ 45 , 46 ]. Components of the ESCRT complex (TSG101 protein) are apparently involved in the formation of microvesicles as well [ 47 ].…”

Section: Biogenesis and Molecular Composition Of Extracellular Vesmentioning

confidence: 99%

Extracellular Vesicles in Viral Pathogenesis: A Case of Dr. Jekyll and Mr. Hyde

Purvinsh

Горшков

Brodskaia

et al. 2021

Life

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Secretion of extracellular vesicles (EVs) is a fundamental property of living cells. EVs are known to transfer biological signals between cells and thus regulate the functional state of recipient cells. Such vesicles mediate the intercellular transport of many biologically active molecules (proteins, nucleic acids, specific lipids) and participate in regulation of key physiological processes. In addition, EVs are involved in the pathogenesis of multiple diseases: infectious, neurodegenerative, and oncological. The current EV classification into microvesicles, apoptotic bodies, and exosomes is based on their size, pathways of cellular biogenesis, and molecular composition. This review is focused on analysis of the role of EVs (mainly exosomes) in the pathogenesis of viral infection. We briefly characterize the biogenesis and molecular composition of various EV types. Then, we consider EV-mediated pro- and anti-viral mechanisms. EV secretion by infected cells can be an important factor of virus spread in target cell populations, or a protective factor limiting viral invasion. The data discussed in this review, on the effect of EV secretion by infected cells on processes in neighboring cells and on immune cells, are of high significance in the search for new therapeutic approaches and for design of new generations of vaccines.

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Actin and Actin-Associated Proteins in Extracellular Vesicles Shed by Osteoclasts

Cited by 32 publications

References 119 publications

Complement C5a Induces Pro-inflammatory Microvesicle Shedding in Severely Injured Patients

Complement C5a Induces Pro-inflammatory Microvesicle Shedding in Severely Injured Patients

The shell matrix and microstructure of the Ram’s Horn squid: Molecular and structural characterization

Extracellular Vesicles in Viral Pathogenesis: A Case of Dr. Jekyll and Mr. Hyde

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