Contribution of ambient airborne particles on the susceptibility to respiratory viral infections.

The respiratory tract is the primary entry point for inhaled particles from anthropogenic or biological origin such as respiratory viruses. Ambient particulate matter (PM) has adverse effects on the respiratory tract through mechanisms eliciting inflammatory responses, oxidative stress, and other pathophysiological effects. At the same time, respiratory viruses cause a range of infections.

Repeated exposures to PM alter the mitochondria and the influenza-mediated interferon response in an air-liquid interface bronchial epithelium.

Humans are exposed to various contaminants, including fine atmospheric particles (PM) and respiratory viruses. Epidemiological studies have demonstrated a positive association between exposure to PM and the severity of viral infections, including those caused by influenza viruses. Nevertheless, there is a paucity of in vitro studies investigating the underlying mechanisms, especially in the context of repeated exposures to PM, which more realistically reflect human exposure.

Exposure to PM modulate the pro-inflammatory and interferon responses against influenza virus infection in a human 3D bronchial epithelium model.

Epidemiological studies showed a positive association between exposure to PM and the severity of influenza virus infection. However, the mechanisms by which PM can disrupt antiviral defence are still unclear. From this perspective, the objective of this study was to evaluate the effects of PM on antiviral signalling in the respiratory epithelium using the bronchial Calu-3 cell line grown at the air-liquid interface.

3D model of the bronchial epithelial barrier to study repeated exposure to xenobiotics: Application to silver nanoparticles.

There is still a lack of in vitro human models to evaluate the chronic toxicity of drugs and environmental pollutants. Here, we used a 3D model of the human bronchial epithelium to assess repeated exposures to xenobiotics. The Calu-3 human bronchial cell line was exposed to silver nanoparticles (AgNP) 5 times during 12 days, at the air-liquid interface, to mimic single and repeated exposure to inhaled particles.

Multiscale investigation of viscoelastic properties of aqueous solutions of sodium alginate and evaluation of their biocompatibility.

In order to get better knowledge of mechanical properties from microscopic to macroscopic scale of biopolymers, viscoelastic bulk properties of aqueous solutions of sodium alginate were studied at different scales by combining macroscopic shear rheology (Hz), diffusing-wave spectroscopy microrheology (kHz-MHz) and Brillouin spectroscopy (GHz). Structural properties were also directly probed by small-angle X-ray scattering (SAXS). The results demonstrate a change from polyelectrolyte behavior to neutral polymer behavior by increasing polymer concentration with the determination of characteristic sizes (persistence length, correlation length).

Effects of brake wear nanoparticles on the protection and repair functions of the airway epithelium.

Long term exposure to particulate air pollution is known to increase respiratory morbidity and mortality. In urban areas with dense traffic most of these particles are generated by vehicles, via engine exhaust or wear processes. Non-exhaust particles come from wear processes such as those concerning brakes and their toxicity is little studied.

Co-culture of type I and type II pneumocytes as a model of alveolar epithelium.

The epithelial tissues of the distal lung are continuously exposed to inhaled air, and are of research interest in studying respiratory exposure to both hazardous and therapeutic materials. Pharmaco-toxicological research depends on the development of sophisticated models of the alveolar epithelium, which better represent the different cell types present in the native lung and interactions between them. We developed an air-liquid interface (ALI) model of the alveolar epithelium which incorporates cell lines which bear features of type I (hAELVi) and type II (NCI-H441) epithelial cells.

Long-term evolution of the epithelial cell secretome in preclinical 3D models of the human bronchial epithelium.

The human bronchial epithelium is the first line of defense against atmospheric particles, pollutants, and respiratory pathogens such as the novel SARS-CoV-2. The epithelial cells form a tight barrier and secrete proteins that are major components of the mucosal immune response. Functional in vitro models of the human lung are essential for screening the epithelial response and assessing the toxicity and barrier crossing of drugs, inhaled particles, and pollutants.

Analysis of Weakly Bound Proteins Reveals Molecular Basis of Soft Corona Formation.

Few experimental techniques allow the analysis of the protein corona . As a result, little is known on the effects of nanoparticles on weakly bound proteins that form the soft corona. Despite its biological importance, our understanding of the molecular bases driving its formation is limited.

Alveolar mimics with periodic strain and its effect on the cell layer formation.

We report on the development of a new model of alveolar air-tissue interface on a chip. The model consists of an array of suspended hexagonal monolayers of gelatin nanofibers supported by microframes and a microfluidic device for the patch integration. The suspended monolayers are deformed to a central displacement of 40-80 µm at the air-liquid interface by application of air pressure in the range of 200-1,000 Pa.

Lung Antioxidant Depletion: A Predictive Indicator of Cellular Stress Induced by Ambient Fine Particles.

Regulations on ambient particulate matter (PM) are becoming more stringent because of adverse health effects arising from PM exposure. PM-induced oxidant production is a key mechanism behind the observed health effects and is heavily dependent on PM composition. Measurement of the intrinsic oxidative potential (OP) of PM could provide an integrated indicator of PM bioreactivity and could serve as a better metric of PM hazard exposure than PM mass concentration.

Mechanisms of Uptake and Translocation of Nanomaterials in the Lung.

Nanomaterials are invading our environment due to their increasing use in a very broad range of sectors making human exposure foreseeable during the life cycle of these materials. Inhalation is one of the most frequent routes of exposure in case of unintentional exposure and the small size of nanomaterials allows them to reach the deep lung. Understanding the fate and effects of nanomaterials is a great challenge for scientists as they exhibit a huge physico-chemical diversity that drives their biological reactivity.

Nanomaterials Versus Ambient Ultrafine Particles: An Opportunity to Exchange Toxicology Knowledge.

Background: A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in models.

Objectives: NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis.

Oxidative potential of particulate matter 2.5 as predictive indicator of cellular stress.

Particulate air pollution being recognized to be responsible for short and long term health effects, regulations for particulate matter with an aerodynamic diameter less than 2.5 (PM) are more and more restrictive. PM regulation is based on mass without taking into account PM composition that drives toxicity.

Assessment of the oxidative potential of nanoparticles by the cytochrome c assay: assay improvement and development of a high-throughput method to predict the toxicity of nanoparticles.

Oxidative stress has increasingly been demonstrated as playing a key role in the biological response induced by nanoparticles (NPs). The acellular cytochrome c oxidation assay has been proposed to determine the intrinsic oxidant-generating capacity of NPs. Yet, there is a need to improve this method to allow a rapid screening to classify NPs in terms of toxicity.

Impact of serum as a dispersion agent for in vitro and in vivo toxicological assessments of TiO nanoparticles.

Nanoparticles (NP) have a tendency to agglomerate after dispersion in physiological media, which can be prevented by the addition of serum. This may however result in modification of the toxic potential of particles due to the formation of protein corona. Our study aimed to analyze the role of serum that is added to improve the dispersion of 10 nm TiO NPs on in vitro and in vivo effects following the exposure via the respiratory route.

The iron component of particulate matter is antiapoptotic: A clue to the development of lung cancer after exposure to atmospheric pollutants?

The classification of outdoor air pollution as carcinogenic for humans strengthens the increasing concern about particulate matter (PM). We previously demonstrated that PM exposure produces an antiapoptotic effect resulting from polycyclic aromatic hydrocarbons (PAH) and water-soluble components. In this study, we investigated transition metallic compounds, particularly iron, in order to decipher their underlying molecular mechanisms that prevent apoptosis.

Metallic oxide nanoparticle translocation across the human bronchial epithelial barrier.

Inhalation is the most frequent route of unintentional exposure to nanoparticles (NPs). Our aim was to quantify the translocation of different metallic NPs across human bronchial epithelial cells and to determine the factors influencing this translocation. Calu-3 cells forming a tight epithelial barrier when grown on a porous membrane in a two compartment chamber were exposed to fluorescently labelled NPs to quantify the NP translocation.

Acute exposure to silica nanoparticles enhances mortality and increases lung permeability in a mouse model of Pseudomonas aeruginosa pneumonia.

Background: The lung epithelium constitutes the first barrier against invading pathogens and also a major surface potentially exposed to nanoparticles. In order to ensure and preserve lung epithelial barrier function, the alveolar compartment possesses local defence mechanisms that are able to control bacterial infection. For instance, alveolar macrophages are professional phagocytic cells that engulf bacteria and environmental contaminants (including nanoparticles) and secrete pro-inflammatory cytokines to effectively eliminate the invading bacteria/contaminants.

Carbon black and titanium dioxide nanoparticles induce distinct molecular mechanisms of toxicity.

Increasing evidence link nanomaterials with adverse biological outcomes and due to the variety of applications and potential human exposures to nanoparticles, it is thus important to evaluate their toxicity for the risk assessment of workers and consumers. It is crucial to understand the underlying mechanisms of their toxicity as observation of similar effects after different nanomaterial exposures does not reflect similar intracellular processing and organelle interactions. A thorough understanding of mechanisms is needed not only for accurate prediction of potential toxicological impacts but also for the development of safer nanoapplications by modulating the physicochemical characteristics.

Development of an in vitro model of human bronchial epithelial barrier to study nanoparticle translocation.

Inhalation is the most frequent route of unintentional exposure to nanoparticles (NPs). Our aim was to compare different in vitro models of human lung epithelial monolayers for their suitability to assess the translocation of 50 nm fluorescently labelled silica NPs (50 nm-SiO(2)-FITC-NPs). Human bronchial epithelial cell lines NCI-H292 and Calu-3 as well as human alveolar cell line A549 were seeded onto Transwell filters (TF) separating the well into an apical and a basal compartment.

[Physio-pathological impacts of inhaled nanoparticles].

Nanomaterials are defined as materials with any external dimension in the nanoscale or having an internal structure or surface structure in the nanoscale, approximately 1 nm to 100 nm. They exhibit new or reinforced properties as compared to the same material at the micrometric scale, providing a benefit in numerous technological applications. However, their specific surface properties in addition to their shape, composition, size are suspected to elicit adverse responses from biological systems, underlining the need for a thorough hazard assessment.

Intracellular signal modulation by nanomaterials.

A thorough understanding of the interactions of nanomaterials with biological systems and the resulting activation of signal transduction pathways is essential for the development of safe and consumer friendly nanotechnology. Here we present an overview of signaling pathways induced by nanomaterial exposures and describe the possible correlation of their physicochemical characteristics with biological outcomes. In addition to the hierarchical oxidative stress model and a review of the intrinsic and cell-mediated mechanisms of reactive oxygen species (ROS) generating capacities of nanomaterials, we also discuss other oxidative stress dependent and independent cellular signaling pathways.

An in vitro assessment of panel of engineered nanomaterials using a human renal cell line: cytotoxicity, pro-inflammatory response, oxidative stress and genotoxicity.

Background: It has been shown that nanomaterials (NMs) are able to translocate to secondary tissues one of the important being the kidneys. Oxidative stress has been implicated as a possible mechanism for NM toxicity, hence effects on the human renal proximal tubule epithelial cells (HK-2) treated with a panel of engineered nanomaterials (NMs) consisting of two zinc oxide particles (ZnO - coated - NM 110 and uncoated - NM 111), two multi walled carbon nanotubes (MWCNT) (NM 400 and NM 402), one silver (NM 300) and five TiO2 NMs (NM 101, NRCWE 001, 002, 003 and 004) were evaluated.

Methods: In order to assess the toxicological impact of the engineered NMs on HK-2 cells - WST-1 cytotoxicity assay, FACSArray, HE oxidation and the comet assays were utilised.