Effet of combined nitrogen dioxide and carbon nanoparticle exposure on lung function during ovalbumin sensitization in brown norway rat

International audienceThe interaction of particulate and gaseous pollutants in their effects on the severity of allergic inflammation and airway responsiveness are not well understood. We assessed the effect of exposure to NO2 in the presence or absence of repetitive treatment with carbon nanoparticle (CNP) during allergen sensitization and challenges in Borwn-Norway (BN) rat, in order to assess their interactions on lung function and airway responses (AR) to allergen and methacholine (MCH), end-expiratory lung volume (EELV), bronchoalveolar lavage fluid (BALF) cellular content, serum and BALF cytokine levels and histological changes. Animals were divided into the following groups (n = 6): Control; CNP (Degussa-FW2): 13 nm, 0.5 mg/kg instilled intratracheally ×3 at 7-day intervals; OVA: ovalbumin-sensitised; OVA+CNP: both sensitized and exposed to CNP. Rats were divided into equal groups exposed either to air or to NO2, 10 ppm, 6 h/d, 5d/wk for 4 weeks. Exposure to NO2, significantly enhanced lung inflammation and airway reactivity, with a significantly larger effect in animals sensitized to allergen, which was related to a higher expression of TH1 and TH2-type cytokines. Conversely, exposure to NO2 in animals undergoing repeated tracheal instillation of CNP alone, increased BALF neutrophilia and enhanced the expression of TH1 cytokines: TNF-a and IFN-?, but did not show an additive effect on airway reactivity in comparison to NO2 alone. The exposure to NO2 combined with CNP treatment and allergen sensitization however, unexpectedly resulted in a significant decrease in both airway reactivity to allergen and to methacholine, and a reduction in TH2-type cytokines compared to allergen sensitization alone. EELV was significantly reduced with sensitization, CNP treatment or both. These data suggest an immunomodulatory effect of repeated tracheal instillation of CNP on the proinflammatory effects of NO2 exposure in sensitized BN rat. Furthermore, our findings suggest that NO2, CNP and OVA sensitization may significantly slow overall lung growth in parenchymally mature animals

Retentissement d'une acidification du milieu sur la glycosylation membranaire de cellules épithéliales de trachée en culture

International audienceLes pluies acides representent une des formes les plus graves de la pollution atmospherique. Elles sont generees essendellement par solubilisation dans l'eau de deux gaz polluants: le S02 qui peut se transformer en acide sulfurique et le dioxide d'azote qui peut generer de l'acide nitrique. Ces acides conferent alors aux precipitations un pH moyen de 3,6 pouvant aller jusqu'a 2 et, de ce fait, contribuent a abaisser le pH de nombreux milieux biologiques. Ceux ci comprennent des ecosystemes entiers (lacs) mais egalement certains tissus humains comme les voies respiratoires. Des etudes ont montre que I'abaissement du pH pouvait jouer un role significatif dans l'alteration de certaines fonctions essentielles pour de nombreuses cellules, en particulier, les cellules epitheliales. Certaines de ces fonctions sont associees ä l'expression membranaire de structures complexes dans lesquelles la partie glucidique est primordiale et, dans ce cas, les acides sialiques sont incrimines

Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines

<p>Abstract</p> <p>Background</p> <p>A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red) and analyzed 2 time points (3 and 24 hours) for each cell type and nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle concentration inducing 50% cell mortality) was calculated.</p> <p>Results</p> <p>The use of MTT assay on THP-1 cells exposed for 24 hours appears to be the most sensitive experimental design to assess the cytotoxic effect of one nanoparticle. With this experimental set-up, Copper- and Zinc-based nanoparticles appear to be the most toxic. Titania, Alumina, Ceria and Zirconia-based nanoparticles show moderate toxicity, and no toxicity was observed for Tungsten Carbide. No correlation between cytotoxicity and equivalent spherical diameter or specific surface area was found.</p> <p>Conclusion</p> <p>Our study clearly highlights the difference of sensitivity between cell types and cytotoxicity assays that has to be carefully taken into account when assessing nanoparticles toxicity.</p

Biodistribution and clearance of instilled carbon nanotubes in rat lung

<p>Abstract</p> <p>Background</p> <p>Constituted only by carbon atoms, CNT are hydrophobic and hardly detectable in biological tissues. These properties make biokinetics and toxicology studies more complex.</p> <p>Methods</p> <p>We propose here a method to investigate the biopersistence of CNT in organism, based on detection of nickel, a metal present in the MWCNT we investigated.</p> <p>Results and conclusion</p> <p>Our results in rats that received MWCNT by intratracheal instillation, reveal that MWCNT can be eliminated and do not significantly cross the pulmonary barrier but are still present in lungs 6 months after a unique instillation. MWCNT structure was also showed to be chemically modified and cleaved in the lung. These results provide the first data of CNT biopersistence and clearance at 6 months after respiratory administration.</p

Decrease in ovalbumin-induced pulmonary allergic response by benzaldehyde but not acetaldehyde exposure in a guinea pig model

International audienceThe pulmonary effects of two environmentally relevant aldehydes were investigated in non-sensitized or ovalbumin (OA)-sensitized guinea pigs (GPs). Four-week-old male Hartley GPs, weighing about 400 g, were intraperitoneally injected with 1 ml of an NaCl solution containing 100 mug OA and 100 mg Al/(OH)(3). They were then exposed to either acetaldehyde (200 ppb) or benzaldehyde (500 ppb) (or 4 wk (6 h/d, 5 d/wk). At the end of exposure, GPs were challenged with an OA aerosol (0.1% in NaCl) and pulmonary functions were measured. The day after, guinea pigs were anesthetized and several endpoints related to inflammatory anti allergic responses were assessed in blood, whole-lung histology, and bronchoalveolar lavage (BAL). Sensitized nonexposed GPs showed bronchial hyperresponsiveness to OA and an increased number of eosinophils in blood and BAL, together with a rise in total protein and leukotrienes (LTB4 and LTC4/D-4/E-4) in BAL. In nonsensitized GPs, exposure to acetaldehyde or benzaldehyde did not induce any change in the tested parameters;, with the exception of irritation of the respiratory tract as detected by histology and an increased number of alveolar macrophages in animals exposed to acetaldehyde. In sensitized GPs, exposure to acetaldehyde induced a moderate irritation of the respiratory tract but no change in biological parameters linked to the inflammatory and allergic responses, In contrast, exposure to benzaldehyde induced a decrease both in OA-induced bronchoconstriction and in eosinophil and neutrophil numbers in BAL, an increase in the bronchodilatator mediator prostaglandin E-2 (PGE(2)) and a decrease in the bronchoconstrictor mediators LTC4/D-4/E-4. Further investigations are needed to determine if the attenuated response observed in sensitized GPs exposed to benzaldehyde is due to an alteration of the mechanism of sensitization or to a more direct effect on various mechanisms of the allergic response

Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats.

International audienceABSTRACT: BACKGROUND: Titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO2 or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms. METHODS: On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg1 pancreatic porcine elastase or saline. On day 7, they received an intratracheal instillation of TiO2 or CB (at 100 and 500 mug) dispersed in bovine serum albumin or bovine serum albumin alone. Animals were sacrificed at days 8 or 21, and bronchoalveolar lavage (BAL) cellularity, histological analysis of inflammation and emphysema, and lung mRNA expression of heme oxygenase-1 (HO-1), interleukin-1beta (IL-1beta), macrophage inflammatory protein-2, monocyte chemotactic protein-1, and matrix metalloprotease (MMP)-1, and -12 were measured. In addition, pulmonary MMP-12 expression was also analyzed at the protein level by immunohistochemistry. RESULTS: TiO2 NPs per se did not modify the parameters investigated, but CB NPs increased perivascular/peribronchial infiltration, and macrophage MMP-12 expression, without inducing emphysema. Elastase administration increased BAL cellularity, histological inflammation, HO-1, IL-1beta and macrophage MMP-12 expression and induced emphysema. Exposure to TiO2 NPs did not modify pulmonary responses to elastase, but exposure to CB NPs aggravated elastase-induced histological inflammation without aggravating emphysema. CONCLUSIONS: TiO2 and CB NPs did not aggravate elastase-induced emphysema. However, CB NPs induced histological inflammation and MMP-12 mRNA and protein expression in macrophages

Immunological Interactive Effects between Pollen Grains and Their Cytoplasmic Granules on Brown Norway Rats

International audienceBackgroundGrass pollen is one of the most important aeroallergen vectors in Europe. Under some meteorological factors, pollen grains can release pollen cytoplasmic granules (PCGs). PCGs induce allergic responses. Several studies have shown that during a period of thunderstorms the number of patients with asthma increases because of higher airborne concentrations of PCGs.ObjectiveThe aims of the study were to assess the allergenicity of interactive effects between pollen and PCGs and to compare it with allergenicity of Timothy grass pollen and PCGs in Brown Norway rats.MethodsRats were sensitized (day 0) and challenged (day 21) with pollen grains and/or PCGs. Four groups were studied: pollen-pollen (PP), PCGs-PCGs (GG), pollen-PCGs (PG), and PCGs-pollen (GP). Blood samples, bronchoalveolar lavage fluid, and bronchial lymph node were collected at day 25. IgE and IgG1 levels in sera were assessed by enzyme-linked immunosorbent assay. Alveolar cells, protein, and cytokine concentrations were quantified in bronchoalveolar lavage fluid. T-cell proliferation, in response to pollen or granules, was performed by lymph node assay.ResultsInteractive effects between pollen and PCGs increased IgE and IgG1 levels when compared with those of the negative control. These increases were lower than those of the PP group but similar to the levels obtained by the GG group. Whatever was used in the sensitization and/or challenge phase, PCGs increased lymphocyte and Rantes levels compared with those of the pollen group. The interactive effects increased IL-1α and IL-1β compared with those of the PP and GG groups.ConclusionsImmunologic interactive effects have been shown between pollen and PCGs. For humoral and cellular allergic responses, interactive effects between the 2 aeroallergenic sources used in this study seem to be influenced mainly by PCGs

Time course of TiO2 and carbon black nanoparticles induced pulmonary inflammationin in rats

Our understanding of how manufactured nanoparticles affect pulmonary immunological response is poor. The aim of the studywas to evaluate, in healthy rats, the acute lung toxicity of intratracheally instilled nanoscale TiO2 (15 nm) and carbon black nanoparticles (Printex 60 and FW2, Degussa). Groups of six rats were instilled once with 100 (micro)g of particles suspended in rat concentrated bronchoalveolar lavage fluid (BALF) as a vehicle. Rats were sacrificed 3, 7 and 21 days post-exposure. ffect assessment included lung histology and markers of lung inflammatory and immunological response. Exposure to FW2 particles induced a significant increase in total alveolar cells after 3 days (4.2×10(6) cells/rat versus 1.8×10(6) cells in control rats). This increase was no more visible at 7 and 21 days. For all groups, alveolar cells consisted mainly in macrophages, with only a slight influx of neutrophils after 7 days exposure to TiO2 and 7 and 21 days to FW2. One day after exposure, the percentage of phagocytosing macrophages was about 14% for TiO2 and P60 and 8% for FW2. The number of macrophages with particles inside remained constant (up to 21 days) for the carbon-based nanoparticles but decreased with time for TiO2 (4.8% at day 21). No TNF-(alpha) was detected either in serum or in BALF of control and exposed-rats. No visible alteration of the lung tissue was noted. As a conclusion, all these particles showed little toxicity in healthy rats in our experimental conditions. FW2 was the most potent to induce a slight but significant inflammatory response

La pollution atmosphérique modifie-t-elle le pouvoir allergisant du pollen de graminées ?

L’allergie est un problème de santé majeur dans la plupart de nos sociétés développées. Il est unanimement reconnu que la prévalence de certaines allergies augmente depuis plusieurs dizaines d’années dans de nombreux pays industrialisés. Les causes de cette augmentation sont encore inconnues, mais, en raison de la rapidité du phénomène, il est admis que des facteurs environnementaux plutôt que génétiques soient impliqués. Parmi ceuxci, la pollution de l’air semble avoir un rôle non négligeable. Les polluants atmosphériques particulaires (en particulier les particules diesel) et gazeux (NO2, O3 et SO2 notamment) sont des facteurs adjuvants connus de la réaction allergique respiratoire. Ils exacerbent la nocivité des allergènes, dont celle des aéroallergènes extérieurs, représentés en majorité par les pollens. En plus de cet effet adjuvant, divers travaux ont montré que l’interaction pollens-polluants aboutissait également à une modification qualitative et quantitative des allergènes de pollens et à une agrégation des pollens avec les polluants particulaires. Durant trois ans, une étude a été menée par l’INERIS, en collaboration avec le centre de recherche RIVM aux Pays-Bas et le laboratoire Environnement et Chimie Analytique de l’École Supérieure de Physique Chimie Industrielle (ESPCI) à Paris, pour déterminer l’impact de la pollution gazeuse sur le potentiel allergisant des pollens de graminée