scholarly journals Crucial Role of Extracellular Vesicles in Bronchial Asthma

2019 ◽  
Vol 20 (10) ◽  
pp. 2589 ◽  
Author(s):  
Tatsuya Nagano ◽  
Masahiro Katsurada ◽  
Ryota Dokuni ◽  
Daisuke Hazama ◽  
Tatsunori Kiriu ◽  
...  

Extracellular vesicles (EVs) are circulating vesicles secreted by various cell types. EVs are classified into three groups according to size, structural components, and generation process of vesicles: exosomes, microvesicles, and apoptotic bodies. Recently, EVs have been considered to be crucial for cell-to-cell communications and homeostasis because they contain intracellular proteins and nucleic acids. Epithelial cells from mice suffering from bronchial asthma (BA) secrete more EVs and suppress inflammation-induced EV production. Moreover, microarray analyses of bronchoalveolar lavage fluid have revealed that several microRNAs are useful novel biomarkers of BA. Mesenchymal stromal cell-derived EVs are possible candidates of novel BA therapy. In this review, we highlight the biologic roles of EVs in BA and review novel EV-targeted therapy to help understanding by clinicians and biologists.

2021 ◽  
Vol 22 (5) ◽  
pp. 2273
Author(s):  
Urszula Demkow ◽  
Anna Stelmaszczyk-Emmel

Currently, extracellular vesicles (EVs) have been implicated in the etiopathogenesis of many diseases, including lung disorders, with the possibility of diagnostic and therapeutic applications. The analysis of EV in respiratory tract diseases faces many obstacles, including material collection from airways, standardization of isolation techniques, detection methods, the analysis of their content, etc. This review focuses on the role of extracellular vesicles in the pathogenesis of atopic respiratory diseases, especially asthma, with a special focus on their clinical applicability as a diagnostic tool. We also summarize available laboratory techniques that enable the detection of EVs in various biological materials, with particular emphasis on flow cytometry. The opportunities and limitations of detecting EV in bronchoalveolar lavage fluid (BALF) were also described.


Author(s):  
Heedoo Lee ◽  
Xue He ◽  
Kareemah Ni ◽  
Jonathan M Carnino ◽  
Yang Jin

Extracellular vesicles (EVs) in bodily fluids play an essential role in cell-cell crosstalk and potentially serve as novel biomarkers in "liquid biopsy". It is crucial to have a consistent, efficient, and reliable method to separate EVs from bodily fluids. Currently, there is no universally accepted, "best" method to separate EVs. Besides differential ultracentrifugation (UC), polyethylene glycol (PEG) is among the commonly used method for EV separation from bodily fluids. However, the optimal concentration of PEG to be used remains inadequately addressed. We initially observed that the concentration of PEG has a significant impact on the amount of separated EVs and EV-cargos which are recovered from bronchoalveolar lavage fluid (BALF). To determine the optimal PEG concentration to be used in EV separation from BALF, we first separated the BALF and serum from wild type C57BL/6 mice. Next, various concentrations of PEG (5, 10, and 15% PEG), a commercial kit, and UC were used to obtain EVs from BALF and serum. EVs were characterized and EV-cargo protein, RNA, and miRNA levels were determined. We found that high concentration of PEG (10% and 15%) altered various EV parameters which are frequently used in EV studies, including EV yield, purity, and morphology. Using miR-15a, -142, and -223 as examples, we found that 10% and 15% PEG robustly reduced the detected levels of EV-cargo miRNAs, compared to those in the EVs separated using UC or 5% PEG. Collectively, low-concentration of PEG facilitates the optimal BALF-EV separation.


2012 ◽  
Vol 113 (9) ◽  
pp. 1476-1485 ◽  
Author(s):  
Ming Zhu ◽  
Alison S. Williams ◽  
Lucas Chen ◽  
Allison P. Wurmbrand ◽  
Erin S. Williams ◽  
...  

The purpose of this study was to examine the role of tumor necrosis factor receptor 1 (TNFR1) in the airway hyperresponsiveness characteristic of obese mice. Airway responsiveness to intravenous methacholine was measured using the forced oscillation technique in obese Cpe fat mice that were either sufficient or genetically deficient in TNFR1 ( Cpe fat and Cpe fat/TNFR1−/− mice) and in lean mice that were either sufficient or genetically deficient in TNFR1 [wild-type (WT) and TNFR1−/− mice]. Compared with lean WT mice, Cpe fat mice exhibited airway hyperresponsiveness. Airway hyperresponsives was also greater in Cpe fat/TNFR1−/− than in Cpe fat mice. Compared with WT mice, Cpe fat mice had increases in bronchoalveolar lavage fluid concentrations of several inflammatory moieties including eotaxin, IL-9, IP-10, KC, MIG, and VEGF. These factors were also significantly elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice. Additional moieties including IL-13 were also elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice but not in Cpe fat vs. WT mice. IL-17A mRNA expression was greater in Cpe fat/TNFR1−/− vs. Cpe fat mice and in TNFR1−/− vs. WT mice. Analysis of serum indicated that obesity resulted in systemic as well as pulmonary inflammation, but TNFR1 deficiency had little effect on this systemic inflammation. Our results indicate that TNFR1 is protective against the airway hyperresponsiveness associated with obesity and suggest that effects on pulmonary inflammation may be contributing to this protection.


Cytokine ◽  
2013 ◽  
Vol 63 (2) ◽  
pp. 194-200 ◽  
Author(s):  
Seigo Okada ◽  
Shunji Hasegawa ◽  
Hideki Hasegawa ◽  
Akira Ainai ◽  
Ryo Atsuta ◽  
...  

2021 ◽  
Vol 8 (11) ◽  
pp. 276
Author(s):  
Chiara Maria Lo Feudo ◽  
Luca Stucchi ◽  
Elena Alberti ◽  
Giovanni Stancari ◽  
Bianca Conturba ◽  
...  

Mild-moderate (MEA), severe (SEA) equine asthma and exercise-induced pulmonary hemorrhage (EIPH) are common respiratory disorders in horses. The present retrospective study aims to evaluate the role of ultrasonography and endoscopy in the diagnosis of these conditions. Three hundred and three horses were included and divided into SEA, MEA and MEA + EIPH groups, on the basis of history, clinical examination and bronchoalveolar lavage fluid (BALf) cytology; scores were assigned to lung ultrasonography, pharyngeal lymphoid hyperplasia (PLH), tracheal mucus (TM) and tracheal bifurcation edema (TB). These scores were compared between groups, and their associations with age, BALf cytology, tracheal wash microbiology and between endoscopic and ultrasonographic scores were statistically analyzed. Ultrasonographic scores were higher in the SEA and MEA + EIPH groups and associated with increased BALf neutrophils and hemosiderophages. The PLH score was higher in younger horses affected by MEA and EIPH and associated with increased eosinophils and hemosiderophages. TM and TB scores were greater in older horses affected by SEA, associated with increased neutrophils and inversely correlated with hemosiderophages. Moreover, TM grade was negatively correlated with mast cells. Thoracic ultrasonography and airway endoscopy can provide useful information about the inflammatory status of upper and lower airways in the horse.


2021 ◽  
Vol 22 (17) ◽  
pp. 9317
Author(s):  
Konstantinos Zifkos ◽  
Christophe Dubois ◽  
Katrin Schäfer

Extracellular vesicles (EVs) compose a heterogenous group of membrane-derived particles, including exosomes, microvesicles and apoptotic bodies, which are released into the extracellular environment in response to proinflammatory or proapoptotic stimuli. From earlier studies suggesting that EV shedding constitutes a cellular clearance mechanism, it has become evident that EV formation, secretion and uptake represent important mechanisms of intercellular communication and exchange of a wide variety of molecules, with relevance in both physiological and pathological situations. The putative role of EVs in hemostasis and thrombosis is supported by clinical and experimental studies unraveling how these cell-derived structures affect clot formation (and resolution). From those studies, it has become clear that the prothrombotic effects of EVs are not restricted to the exposure of tissue factor (TF) and phosphatidylserines (PS), but also involve multiplication of procoagulant surfaces, cross-linking of different cellular players at the site of injury and transfer of activation signals to other cell types. Here, we summarize the existing and novel clinical and experimental evidence on the role and function of EVs during arterial and venous thrombus formation and how they may be used as biomarkers as well as therapeutic vectors.


2019 ◽  
Vol 317 (5) ◽  
pp. G739-G749 ◽  
Author(s):  
Harmeet Malhi

Extracellular vesicles (EVs) are membrane-defined nanoparticles released by most cell types. The EVs released by cells may differ quantitatively and qualitatively from physiological states to disease states. There are several unique properties of EVs, including their proteins, lipids and nucleic acid cargoes, stability in circulation, and presence in biofluids, which make them a critical vector for cell-to-cell communication and impart utility as a biomarker. EVs may also serve as a vehicle for selective cargo secretion. Similarly, EV cargo may be selectively manipulated for targeted therapeutic delivery. In this review an overview is provided on the EV classification, biogenesis, and secretion pathways, which are conserved across cell types. Next, cargo characterization and effector cell responses are discussed in the context of nonalcoholic steatohepatitis, alcoholic hepatitis, and acetaminophen-induced liver injury. The review also discusses the potential biomarker and therapeutic uses of circulating EVs.


2018 ◽  
Vol 2 (S1) ◽  
pp. 33-33
Author(s):  
Elizabeth L. Kramer ◽  
William Hardie ◽  
Kristin Hudock ◽  
Cynthia Davidson ◽  
Alicia Ostmann ◽  
...  

OBJECTIVES/SPECIFIC AIMS: Transforming growth factor-beta (TGFβ) is a genetic modifier of cystic fibrosis (CF) lung disease. TGFβ’s pulmonary levels in young CF patients and its mechanism of action in CF are unknown. We examined TGFβ levels in children with CF and investigated responses of human airway epithelial cells (AECs) and mice to TGFβ. METHODS/STUDY POPULATION: TGFβ levels in bronchoalveolar lavage fluid from CF patients (n=15) and non-CF control patients (n=21)<6 years old were determined by ELISA. CF mice and non-CF mice were intratracheally treated with an adenoviral TGFβ1 vector or PBS; lungs were collected for analysis at day 7. Human CF and non-CF AECs were treated with TGFβ or PBS for 24 hours then collected for analysis. RESULTS/ANTICIPATED RESULTS: Young CF patients had higher bronchoalveolar lavage fluid TGFβ than non-CF controls (p=0.03). Mouse lungs exposed to TGFβ demonstrated inflammation, goblet cell hyperplasia, and decreased CFTR expression. CF mice had greater TGFβ-induced lung mechanics abnormalities than controls; both CF human AECs and CF mice showed higher TGFβ induced MAPK and PI3K signaling compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: For the first time, we show increased TGFβ levels very early in CF. TGFβ drives CF lung abnormalities in mouse and human models; CF models are more sensitive to TGFβ’s effects. Understanding the role of TGFβ in promoting CF lung disease is critical to developing patient specific treatments.


2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338 ◽  
Author(s):  
Sara Pączek ◽  
Marta Łukaszewicz-Zając ◽  
Barbara Mroczko

Colorectal cancer (CRC) is one of the leading causes of cancer-related death. It is the second most frequently diagnosed malignancy in Europe and third worldwide. Colorectal malignancies diagnosed at an early stage offer a promising survival rate. However, advanced tumors often present distant metastases even after the complete resection of a primary tumor. Therefore, novel biomarkers of CRC are sorely needed in the diagnosis and prognosis of this common malignancy. A family of chemokines are composed of small, secreted proteins. They are best known for their ability to stimulate the migration of several cell types. Some investigations have indicated that chemokines are involved in cancer development, including CRC. This article presents current knowledge regarding chemokines and their specific receptors in CRC progression. Moreover, the prime aim of this review is to summarize the potential role of these proteins as biomarkers in the diagnosis and prognosis of CRC.


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