Large Extracellular Vesicles: Have We Found the Holy Grail of Inflammation?

Słomka, Artur; Urban, Sabine; Lukacs‐Kornek, Veronika; Żekanowska, Ewa; Kornek, Miroslaw

doi:10.3389/fimmu.2018.02723

Cited by 131 publications

(135 citation statements)

References 298 publications

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“…EVs are often important for animals and humans, especially when afflicted by infectious diseases. It appears, therefore, that the EV cocktails from the blood or other origin can induce apparently opposite effects, programmed towards pro-or antiinflammatory cell phenotypes [23,[27][28][29][30][31][32]. The EVs most effective for intervention in the latter responses are those derived from mesenchymal stromal cells (MSCs) [26].…”

Section: Immune Cell Diseasesmentioning

confidence: 99%

“…Such approaches, not yet fully standardized, have already been successfully employed in humans [30,64]. In infectious diseases, EVs from MSCs are employed as novel therapeutic tools.…”

Section: Diagnosis and Therapymentioning

confidence: 99%

“…However, effects induced by miscellaneous EVs have also been of antiinflammatory type. It appears, therefore, that the EV cocktails from the blood or other origin can induce apparently opposite effects, programmed towards pro-or antiinflammatory cell phenotypes [23,[27][28][29][30][31][32].…”

Section: Immune Cell Diseasesmentioning

confidence: 99%

“…In fact, they suppress proinflammatory processes, also reducing oxidative stress and fibrosis with concomitant tissue regeneration, allowing endogenous stem and progenitor cells to repair affected tissues. Such approaches, not yet fully standardized, have already been successfully employed in humans [30,64]. EVs from MSCs are also of interest for treatment of brain degenerative diseases.…”

Section: Diagnosis and Therapymentioning

confidence: 99%

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

Meldolesi

2019

Clinical and Experimental Immunology

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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.

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Section: Immune Cell Diseasesmentioning

confidence: 99%

“…Such approaches, not yet fully standardized, have already been successfully employed in humans [30,64]. In infectious diseases, EVs from MSCs are employed as novel therapeutic tools.…”

Section: Diagnosis and Therapymentioning

confidence: 99%

Section: Immune Cell Diseasesmentioning

confidence: 99%

Section: Diagnosis and Therapymentioning

confidence: 99%

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

Meldolesi

2019

Clinical and Experimental Immunology

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“…In recent years, there has been a growing interest to improve current knowledge of the nature, constitution and biogenesis of all secreted EVs. Lately, the field of EVs is debating the need to accurately separate EV subtypes to investigate functional relevance (Tckach et al, 2018; Slomka et al, 2018). Enrichment of subpopulations of EVs from samples is acquired based on differential centrifugation steps: large EVs (LEVs) are obtained at speeds lower than 20,000xg and small EVs (SEVs) are pelleted at 100.000xg in a further ultracentrifugation step.…”

Section: Introductionmentioning

confidence: 99%

Peptidylarginine Deiminase inhibition abolishes the production of large extracellular vesicles fromGiardia intestinalis, affecting host-pathogen interactions by hindering adhesion to host cells

Gavinho

Rossi

Evans-Osses

et al. 2019

Preprint

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Giardia intestinalis is an anaerobic protozoan that is an important etiologic agent of inflammation-driven diarrhea worldwide. Although self-limiting, a deep understanding of the factors involved in the pathogenicity that produces the disruption of the intestinal barrier remains unknown. There is evidence that under diverse conditions, the parasite is capable of shedding extracellular vesicles (EVs) which could modulate the physiopathology of giardiasis. Here we describe new insights of G. intestinalis EV production, revealing its capacity to shed two different enriched EV populations (large and small extracellular vesicles) and identified a relevant adhesion function associated only with the larger population. Our work also aimed at assessing the influences of two recently identified inhibitors of EV release in mammalian cells, namely peptidylarginine deiminase (PAD) inhibitor and cannabidiol (CBD), on EV release from Giardia and their putative effects on host-pathogen interactions. PAD-inhibitor Cl-amidine and CBD were both able to effectively reduce EV shedding, the PAD-inhibitor specifically affecting the release of large extracellular vesicles and interfering with in vitro host-pathogen interactions. The strong efficacy of the PAD-inhibitor on Giardia EV release indicates a phylogenetically conserved pathway of PAD-mediated EV release, most likely affecting the Giardia arginine deiminase (GiADI) homolog of mammalian PADs. While there is still much to learn about G. intestinalis interaction with its host, our results suggest that large and small EVs may be differently involved in protozoa communication, and that EV-inhibitor treatment may be a novel strategy for recurrent giardiasis treatment.

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Association of plasma pentraxin 3 concentration with angiographic and clinical outcomes in patients with acute ST‐segment elevation myocardial infarction treated by primary angioplasty

Dharma

Sari

Santoso

et al. 2019

Cathet Cardio Intervent

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Objective: To evaluate the association of plasma long pentraxin 3 (PTX3) concentration with angiographic and clinical outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI) treated by primary angioplasty. Background: Whether concentration of PTX3, a sensitive marker of inflammation, associates with angiographic and clinical outcomes in STEMI patients treated by primary angioplasty is unknown. Methods: We prospectively enrolled 335 consecutive patients with acute STEMI undergoing primary angioplasty. Blood samples for plasma PTX3 measurement were drawn in all patients at the emergency department before primary angioplasty, and were measured by ELISA method. Results: The median PTX3 concentrations were higher in patients with thrombus burden grade 4 and 5 versus grade <4 on initial coronary angiogram (0.29 ng/ml vs. 0.24 ng/ml, p = .02), thrombolysis in myocardial infarction (TIMI) grade <3 vs. TIMI grade-3 flow after primary angioplasty (0.31 ng/ml vs. 0.24 ng/ml, p < .001), incomplete versus complete ST-segment resolution within 12 hr after angioplasty (0.29 ng/ml vs. 0.22 ng/ml, p = .001) and in patients who did not survive versus those who survived at 30 days (0.44 ng/ml vs. 0.26 ng/ml, p = .001). A linear correlation was observed between PTX3 concentration and baseline leukocyte count (Spearman correlation = 0.21, p < .001). After adjustment for laboratory and selected clinical variables, patients in the highest quartile of PTX3 concentration (≥0.4 ng/ml) were associated with increased risk of 30-day mortality (hazard ratio = 11.83; 95% confidence interval = 1.52-92.27, p = .01). Conclusion: This study suggests that higher plasma PTX3 concentration associates with worse angiographic and clinical outcomes in STEMI patients treated by primary angioplasty.

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Large Extracellular Vesicles: Have We Found the Holy Grail of Inflammation?

Cited by 131 publications

References 298 publications

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

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

Peptidylarginine Deiminase inhibition abolishes the production of large extracellular vesicles fromGiardia intestinalis, affecting host-pathogen interactions by hindering adhesion to host cells

Association of plasma pentraxin 3 concentration with angiographic and clinical outcomes in patients with acute ST‐segment elevation myocardial infarction treated by primary angioplasty

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