Absence of phagolysosomal activation and high clearance efficiency define the low pulmonary toxicity of short asbestos fibers.

The physicochemical properties of fibers critically determine asbestos pathogenicity, driving inflammation, fibrosis, and lung cancer. The prevailing paradigm in fiber toxicology posits that long and biopersistent fibers pose a greater health risk than short fibers. However, this assumption is debated due to limited studies specifically assessing the pathogenicity of short fibers.

Transcriptomic profile of TiO particle overload in rat alveolar macrophages: examining responses between P25 and two pigment grade particles in vitro.

The industrial uses of titanium dioxide (TiO) are extensive, with pigment grades (particle size > 100 nm) being the most common forms produced. Nanoforms (particle size < 100 nm) of TiO (e.g.

Unique transcriptomic responses of rat and human alveolar macrophages in an in vitro model of overload with TiO and carbon black.

Background: Chronic inhalation of titanium dioxide or carbon black can lead, at high exposure, to lung overload, and can induce chronic inflammation and lung cancer in rats. Whether this rat adverse response is predictive for humans has been questioned for more than 40 years. Currently, these particles are conservatively considered as possible human carcinogens.

Dynamic biodistribution of inhaled silica particles to extrapulmonary sites: Early and late translocation mechanisms with implication for particle biomonitoring.

An innovative method based on inductively coupled plasma mass spectrometry (ICP-MS) was developed to quantify the time-dependent systemic redistribution pattern of pulmonary-deposited crystalline silica particles by measuring silicon (Si) levels in the lungs, distal organs, and biological fluids. The method was applied in a murine model and validated in blood and urine samples from two occupationally exposed cohorts (miners and porcelain industry workers). In mice, 30 % of silica particles deposited in the lungs via oropharyngeal administration accumulated in extrapulmonary sites in less than 4 months.

Pulmonary and systemic effects of inhaled crystalline silica in the HOCl-induced mouse model of systemic sclerosis: An experimental model of Erasmus syndrome.

Occupational exposure to crystalline silica is etiologically linked to an increased incidence of systemic sclerosis (SSc), also called Erasmus syndrome. The underlying mechanisms of silica-related SSc are still poorly understood. We demonstrated that early and repeated silica exposure contribute to the severity of SSc symptoms in the hypochloric acid (HOCl)-induced SSc mouse model.

Distinct Pro-Inflammatory Mechanisms Elicited by Short and Long Amosite Asbestos Fibers in Macrophages.

While exposure to long amphibolic asbestos fibers (L > 10 µm) results in the development of severe diseases including inflammation, fibrosis, and mesothelioma, the pathogenic activity associated with short fibers (L < 5 µm) is less clear. By exposing murine macrophages to short (SFA) or long (LFA) fibers of amosite asbestos different in size and surface chemistry, we observed that SFA internalization resulted in pyroptotic-related immunogenic cell death (ICD) characterized by the release of the pro-inflammatory damage signal (DAMP) IL-1α after inflammasome activation and gasdermin D (GSDMD)-pore formation. In contrast, macrophage responses to non-internalizable LFA were associated with tumor necrosis factor alpha (TNF-α) release, caspase-3 and -7 activation, and apoptosis.

Gasdermin D membrane pores orchestrate IL-1α secretion from necrotic macrophages after NFS-rich silica exposure.

IL-1α is an intracellular danger signal (DAMP) released by macrophages contributing to the development of silica-induced lung inflammation. The exact molecular mechanism orchestrating IL-1α extracellular release from particle-exposed macrophages is still unclear. To delineate this process, murine J774 and bone-marrow derived macrophages were exposed to increasing concentrations (1-40 cm/ml) of a set of amorphous and crystalline silica particles with different surface chemical features.

Monocytic Ontogeny of Regenerated Macrophages Characterizes the Mesotheliomagenic Responses to Carbon Nanotubes.

Macrophages are not only derived from circulating blood monocytes or embryonic precursors but also expand by proliferation. The origin determines macrophage fate and functions in steady state and pathological conditions. Macrophages predominantly infiltrate fibre-induced mesothelioma tumors and contribute to cancer development.

Dietary nanoparticles alter the composition and function of the gut microbiota in mice at dose levels relevant for human exposure.

Background: Nanotechnologies provide new opportunities for improving the safety, quality, shelf life, flavor and appearance of foods. The most common nanoparticles (NPs) in human diet are silver metal, mainly present in food packaging and appliances, and silicon and titanium dioxides used as additives. The rapid development and commercialization of consumer products containing these engineered NPs is, however, not well supported by appropriate toxicological studies and risk assessment.

Systemic effects and impact on the gut microbiota upon subacute oral exposure to silver acetate in rats.

Context: The addition of silver (Ag) to food items, and its migration from food packaging and appliances results in a dietary exposure in humans, estimated to 70-90 µg Ag/day. In view of the well-known bactericidal activity of Ag ions, concerns arise about a possible impact of dietary Ag on the gut microbiota (GM), which is a master determinant of human health and diseases. Repeated oral administration of Ag acetate (AgAc) can also cause systemic toxicity in rats with reported NOAELs of 4 mg AgAc/b.

Nearly free surface silanols are the critical molecular moieties that initiate the toxicity of silica particles.

Inhalation of silica particles can induce inflammatory lung reactions that lead to silicosis and/or lung cancer when the particles are biopersistent. This toxic activity of silica dusts is extremely variable depending on their source and preparation methods. The exact molecular moiety that explains and predicts this variable toxicity of silica remains elusive.

and Toxicity Studies on Chiov. Leaves Essential Oil from Benin.

Chiov. (Poaceae) is a medicinal plant used to treat various diseases in traditional medicine in several African countries. The present study aims to evaluate the oral and inhalation toxicity as well as the mutagenic effects of the essential oil of leaves (EOCG) from a sample collected in Benin.

LiCoO particles used in Li-ion batteries induce primary mutagenicity in lung cells via their capacity to generate hydroxyl radicals.

Background: Li-ion batteries (LIB) are used in most portable electronics. Among a wide variety of materials, LiCoO (LCO) is one of the most used for the cathode of LIB. LCO particles induce oxidative stress in mouse lungs due to their Co content, and have a strong inflammatory potential.

Respiratory hazard of Li-ion battery components: elective toxicity of lithium cobalt oxide (LiCoO) particles in a mouse bioassay.

Rechargeable Li-ion batteries (LIB) are increasingly produced and used worldwide. LIB electrodes are made of micrometric and low solubility particles, consisting of toxicologically relevant elements. The health hazard of these materials is not known.

New interplay between interstitial and alveolar macrophages explains pulmonary alveolar proteinosis (PAP) induced by indium tin oxide particles.

Occupational exposure to indium tin oxide (ITO) particles has been associated with the development of severe lung diseases, including pulmonary alveolar proteinosis (PAP). The mechanisms of this lung toxicity remain unknown. Here, we reveal the respective roles of resident alveolar (Siglec-F AM) and recruited interstitial (Siglec-F IM) macrophages contributing in concert to the development of PAP.

CCR2 monocytic myeloid-derived suppressor cells (M-MDSCs) inhibit collagen degradation and promote lung fibrosis by producing transforming growth factor-β1.

Monocytes infiltrating scar tissue are predominantly viewed as progenitor cells. Here, we show that tissue CCR2 monocytes have specific immunosuppressive and profibrotic functions. CCR2 monocytic cells are acutely recruited to the lung before the onset of silica-induced fibrosis in mice.

PET/CT with 18F-FDG- and 18F-FBEM-labeled leukocytes for metabolic activity and leukocyte recruitment monitoring in a mouse model of pulmonary fibrosis.

Unlabelled: Idiopathic pulmonary fibrosis is characterized by a progressive and irreversible respiratory failure. Validated noninvasive methods able to assess disease activity are essential for prognostic purposes as well as for the evaluation of emerging antifibrotic treatments.

Methods: C57BL/6 mice were used in a murine model of pulmonary fibrosis induced by an intratracheal instillation of bleomycin (control mice were instilled with a saline solution).

The alarmin IL-1α is a master cytokine in acute lung inflammation induced by silica micro- and nanoparticles.

Background: Inflammasome-activated IL-1β plays a major role in lung neutrophilic inflammation induced by inhaled silica. However, the exact mechanisms that contribute to the initial production of precursor IL-1β (pro-IL-1β) are still unclear. Here, we assessed the implication of alarmins (IL-1α, IL-33 and HMGB1) in the lung response to silica particles and found that IL-1α is a master cytokine that regulates IL-1β expression.

Nanometer-long Ge-imogolite nanotubes cause sustained lung inflammation and fibrosis in rats.

Background: Ge-imogolites are short aluminogermanate tubular nanomaterials with attractive prospected industrial applications. In view of their nano-scale dimensions and high aspect ratio, they should be examined for their potential to cause respiratory toxicity. Here, we evaluated the respiratory biopersistence and lung toxicity of 2 samples of nanometer-long Ge-imogolites.

IL-1α induces CD11b(low) alveolar macrophage proliferation and maturation during granuloma formation.

Macrophages play a central role in immune and tissue responses of granulomatous lung diseases induced by pathogens and foreign bodies. Circulating monocytes are generally viewed as central precursors of these tissue effector macrophages. Here, we provide evidence that granulomas derive from alveolar macrophages serving as a local reservoir for the expansion of activated phagocytic macrophages.

Uncoupling between inflammatory and fibrotic responses to silica: evidence from MyD88 knockout mice.

The exact implication of innate immunity in granuloma formation and irreversible lung fibrosis remains to be determined. In this study, we examined the lung inflammatory and fibrotic responses to silica in MyD88-knockout (KO) mice. In comparison to wild-type (WT) mice, we found that MyD88-KO animals developed attenuated lung inflammation, neutrophil accumulation and IL-1β release in response to silica.