Pulmonary Extracellular Vesicles as Mediators of Local and Systemic Inflammation

Wahlund, Casper J. E.; Eklúnd, Anders; Grünewald, Johan; Gabrielsson, Susanne

doi:10.3389/fcell.2017.00039

Cited by 66 publications

(68 citation statements)

References 79 publications

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“…Exosome cargo composition is highly affected by cellular homeostasis and pathology (Hooper et al 2012; Prieto et al 2017; Selmaj et al 2017; Wahlund et al 2017). As discussed in this review, toxic Aβ peptides and toxic species of P-Tau, neuroinflammation, and oxidative stress can all alter exosome content, secretion rate, and the cell-to-cell messages they carry.…”

Section: Resultsmentioning

confidence: 99%

“…Gupta and Pulliam, 2014). Exosomes are capable of inducing pro-inflammatory effects, including antigen presentation, cellular migration, apoptosis induction, and inflammatory cytokine release (Wahlund et al 2017). They can cross the blood-brain barrier to contribute to the spread of brain antigens from the periphery to the brain, or vice versa (Selmaj et al 2017).…”

Section: Introductionmentioning

confidence: 99%

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Exosomal biomarkers in Down syndrome and Alzheimer's disease

Hamlett

Ledreux

Potter³

et al. 2018

Free Radical Biology and Medicine

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Every person with Down syndrome (DS) has the characteristic features of Alzheimer’s disease (AD) neuropathology in their brain by the age of forty, and most go on to develop AD dementia. Since people with DS show highly variable levels of baseline function, it is often difficult to identify early signs of dementia in this population. The discovery of blood biomarkers predictive of dementia onset and/or progression in DS is critical for developing effective clinical diagnostics. Our recent studies show that neuron-derived exosomes, which are small extracellular vesicles secreted by most cells in the body, contain elevated levels of amyloid-beta peptides and phosphorylated-Tau that could indicate a preclinical AD phase in people with DS starting in childhood. We also found that the relative levels of these biomarkers were altered following dementia onset. Exosome release and signaling are dependent on cellular redox homeostasis as well as on inflammatory processes, and exosomes may be involved in the immune response, suggesting a dual role as both triggers of inflammation in the brain and propagators of inflammatory signals between brain regions. Based on recently reported connections between inflammatory processes and exosome release, the elevated neuroinflammatory state observed in people with DS may affect exosomal AD biomarkers. Herein, we discuss findings from studies of people with DS, people with DS and AD (DS-AD), and mouse models of DS showing new connections between neuroinflammatory pathways, oxidative stress, exosomes, and exosome-mediated signaling, which may inform future AD diagnostics, preventions, and treatments in the DS population as well as in the general population.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exosomal biomarkers in Down syndrome and Alzheimer's disease

Hamlett

Ledreux

Potter³

et al. 2018

Free Radical Biology and Medicine

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show abstract

“…In the Mor− group, the positive associations between both PM10 and PM2.5 levels and plasmatic EV could be partially explained by the presence of a heterogeneous NMB. Interestingly, both CD14+ and CD105+ EVs were the most abundant ones, probably due to the fact that, after deposition on alveolar epithelium, PM can be phagocyted by macrophages, pass through the alveolar-capillary membrane, and directly interact with pulmonary endothelium [45], stimulating these sources of EVs production.…”

Section: Discussionmentioning

confidence: 99%

Nasal Microbiota Modifies the Effects of Particulate Air Pollution on Plasma Extracellular Vesicles

Mariani

Favero

Carugno

et al. 2020

IJERPH

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Air pollution exposure has been linked to modifications of both extracellular vesicle (EV) concentration and nasal microbiota structure (NMB), which might act as the respiratory health gatekeeper. This study aimed to assess whether an unbalanced NMB could modify the effect of particulate matter (PM) exposure on plasmatic EV levels. Due to two different NMB taxonomical profiles characterized by a widely different relative abundance of the Moraxella genus, the enrolled population was stratified into Mor− (balanced NMB) and Mor+ (unbalanced NMB) groups (Moraxella genus’s cut-off ≤25% and >25%, respectively). EV features were assessed by nanoparticle tracking analysis (NTA) and flow-cytometry (FC). Multivariable analyses were applied on EV outcomes to evaluate a possible association between PM10 and PM2.5 and plasmatic EV levels. The Mor− group revealed positive associations between PM levels and plasmatic CD105+ EVs (GMR = 4.39 p = 0.02) as for total EV count (GMR = 1.92 p = 0.02). Conversely, the Mor+ group showed a negative association between exposure and EV outcomes (CD66+ GMR = 0.004 p = 0.01; EpCAM+ GMR = 0.005 p = 0.01). Our findings provide an insight regarding how a balanced NMB may help to counteract PM exposure effects in terms of plasmatic EV concentration. Further research is necessary to understand the relationship between the host and the NMB to disentangle the mechanism exerted by inhaled pollutants in modulating EVs and NMB.

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“…Cells secrete signaling molecules (e.g., interleukins) and extracellular vesicles (EVs) (e.g., exosomes) across the basement membrane under both homeostatic and pathological conditions, but also in response to environmental challenges including pathogens, gaseous irritants, cigarette smoke, and environmental particles . Monitoring of these cell signaling processes is vital for understanding the role of cell signaling in disease development and requires the use of porous membrane.…”

Section: Alveolar‐capillary Basement Membrane For Ali Cell Culturesmentioning

confidence: 99%

Evolution of Bioengineered Lung Models: Recent Advances and Challenges in Tissue Mimicry for Studying the Role of Mechanical Forces in Cell Biology

Doryab

Taş

Taskin

et al. 2019

Adv Funct Materials

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Mechanical stretch under both physiological (breathing) and pathophysiological (ventilator-induced) conditions is known to significantly impact all cellular compartments in the lung, thereby playing a pivotal role in lung growth, regeneration and disease development. In order to evaluate the impact of mechanical forces on the cellular level, in vitro models using lung cells on stretchable membranes have been developed. Only recently have some of these cell-stretching devices become suitable for air-liquid interface cell cultures, which is required to adequately model physiological conditions for the alveolar epithelium. To reach this goal, a multi-functional membrane for cell growth balancing biophysical and mechanical properties is critical to mimic (patho)physiological conditions. In this review, i) the relevance of cyclic mechanical forces in lung biology is elucidated, ii) the physiological range for the key parameters of tissue stretch in the lung is described, and iii) the currently available in vitro cell-stretching devices are discussed. After assessing various polymers, it is concluded that natural-synthetic copolymers are promising candidates for suitable stretchable membranes used in cell-stretching models. This work provides guidance on future developments in biomimetic in vitro models of the lung with the potential to function as a template for other organ models (e.g., skin, vessels).

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Pulmonary Extracellular Vesicles as Mediators of Local and Systemic Inflammation

Cited by 66 publications

References 79 publications

Exosomal biomarkers in Down syndrome and Alzheimer's disease

Exosomal biomarkers in Down syndrome and Alzheimer's disease

Nasal Microbiota Modifies the Effects of Particulate Air Pollution on Plasma Extracellular Vesicles

Evolution of Bioengineered Lung Models: Recent Advances and Challenges in Tissue Mimicry for Studying the Role of Mechanical Forces in Cell Biology

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