Ozone et système immunitaire

National audienceThis review focuses on rite effect on health of changes in the immune system secondary to ozone exposure and on various mechanistic hypotheses pur forward. Beyond the problems related to the variability of study criteria (e.g. age, sex, concentration and duration of different types of exposure, the slightly volatile nature of ozone and the complexity of the immune system), ozone may induce immunostimulation as shown by intensified allergic phenomena of immunosuppression expressed by increased sensitivity to bacterial infections. Different functions of the immune response (Sor example macrophage and polynuclear phagocytic and bactericidal activity, NK activity, cytokine and antibody production...) are affected. In terms of risk, the consequences of these changes depend on their intensity, their perennial nature and their association with particular genetic characteristics or other forms of external aggression, for example infection. The effect of exposure to a mixture of pollutants with unknown interactions should also be taken into consideration. Finally, the problem of normal bur possibly exaggerated immune response to a compound whose allergenicity may have been modified by ozone must also be taken into accountCette revue fait le point sur les altérations de la santé attribuables à des perturbations du Système Immunitaire consécutives à une exposition à l'ozone ainsi que sur les diverses hypothèses mécanistiques étudiées. Au-delà des problèmes posés par des critères de variabilité (âge, sexe, concentration et durée d'exposition différentes, caractère peu rémanent de l'ozone, complexité du système immunitaire...) l'ozone peut induire une immunostimulation se manifestant par une intensification des phénomènes allergiques ou une immunosuppression caractérisée par une augmentation de la sensibilité aux infections bactériennes. Des fonctions de différents acteurs de la réponse immunitaire sont atteintes: capacité de phagocytose et de bactéricidie par les macrophages et polynucléaires, activité NK production de cytokines, d'anticorps... En terme de risque, les conséquences de ces altérations dépendront de leur intensité, de leur pérennité et de leur association avec des caractères génétiques particuliers ou avec d'autres agressions, par exemple d'origines infectieuses. De même, il faut considérer que nous sommes souvent exposés à un mélange de polluants dont les interactions nous restent, à ce jour, inconnues. Il faut enfin évoquer le problème de la réponse, normale mais éventuellement exacerbée, du système immunitaire à un composé dont l'allergénicité peut avoir été modifiée par l'ozon

Aspects médicaux de l'exposition aux oxydes d'azote

Les oxydes d'azote sont souvent désignés par la formule générale NOx. On considère que parmi eux, seuls le monoxyde d'azote (NO) et le dioxyde d'azote (NO2, aussi appelé peroxyde d'azote) représentent un risque potentiel pour la santé

Decreased Sialidase Activity in Alveolar Macrophages of Guinea Pigs Exposed to Coal Mine Dust

International audienceThe origin of immune dysfunctions that are observed in pneumoconiotic miners still remains unknown. There is evidence that the carbohydrate moiety of membrane glycoconjugates is of primary importance in many functions of immunocompetent cells. The glycosylation, and especially the sialylation level of membrane components of various lymphocyte and macrophage subsets, vary depending on the state of cellular differentiation and activation. Sialidases, which may regulate the amount of sialic acids exposed on the cell membrane, can thus be considered as immunoregulatory enzymes. In this report, the sialidase activity has been measured in alveolar macrophages (AM) and in cell-free bronchoalveolar lavage fluid (BALF) from guinea pigs exposed for 4 months to coal mine dust at a concentration of 300 mg/m3. The samples were collected by bronchoalveolar lavage 2 months after cessation of exposure. The sialidase activity in the cell-free fluid and in the purified alveolar macrophages showed a 10-fold decrease (p < 0.001). Kinetic parameters of the enzyme such as K(m) and optimum pH did not change. This changed activity was specific for sialidase, as two other lysosomal glycosidases, beta-galactosidase and N-acetylglucosaminidase, showed unchanged activities. These results suggest the possibility that, by inducing a decreased sialidase activity, exposure to coal mine dust may lead to a modified expression of AM membrane-associated sialic acids giving rise to altered immune functions (i. e., phagocytosis, antigen processing response to cytokines, etc.)

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

Induction of the HSP70 gene promoter by various anticancer drugs

International audienceHeLa cells containing the chloramphenicol acetyl transferase (CAT) gene under the control of the hsp70 promoter have been exposed in vitro to various anticancer drugs. Cisplatin induced CAT production with a dose-effect relationship at a non-cytotoxic dose, whereas no induction was detected with carboplatin. Etoposid induced a significant response at a cytotoxic concentration. The limited positive response with doxorubicin, daunomycin and mitoxantrone was not statistically significant. These chemicals are known to produce reactive oxygen species and induce apoptosis. No induction of the hsp70 promoter could be detected with the other cytostatic compounds that have been tested such as base analogues (5-fluorouracil, cytosine arabinoside 3'-MP), inhibitors of DNA synthesis (amethopterin, aminopterin), antimitotics (vinblastine, colchicine), and alkylating (streptozotocine, carboplatin, melphalan) or intercalating agents (bleomycin). In addition, the role of the transcription inhibitory activity of doxorubicin in this model is evidenced and the consequent question of the suitability of the reporter gene system is discussed. Our results suggest that specific genotoxic compounds are not able to induce the hsp70 promoter, and are in agreement with the concept that stimulation of HSP70 synthesis occurs through a biochemical process involving proteotoxicity

Updated safety evaluation of the food enzyme isoamylase from the Dyella sp. strain MU 1174

[EN] The food enzyme isoamylase (glycogen ¿-1,6-glucanohydrolase, EC 3.2.1.68) is produced with Dyella sp. strain MU 1174 by Hayashibara Co. Ltd. In a previous opinion, the Panel on Food Contact Materials, Enzymes and Processing Aids of EFSA could not conclude on the safety of this food enzyme due to uncertainties about the presence of a gene conferring resistance to antimicrobials in the genome of the production strain and its potential transfer to the food enzyme. New whole genome sequence data provided by the applicant showed that the production strain Dyella sp. MU 1174 does not contain antimicrobial resistance genes of concern. Based on the new data provided and the evaluation of the data previously submitted, the Panel concludes that this food enzyme does not give rise to safety concerns under the intended conditions of use.Lambre, C.; Barat Baviera, JM.; Bolognesi, C.; Cocconcelli, PS.; Crebelli, R.; Gott, DM.; Grob, K.... (2021). Updated safety evaluation of the food enzyme isoamylase from the Dyella sp. strain MU 1174. EFSA Journal. 19(10):1-7. https://doi.org/10.2903/j.efsa.2021.6871S17191

Safety evaluation of a food enzyme containing trypsin, chymotrypsin, elastase and carboxypeptidase from porcine pancreas

[EN] The food enzyme is a protease complex, containing trypsin (EC 3.4.21.4), chymotrypsin (EC 3.4.21.1), pancreatic elastase (EC 3.4.21.36) and carboxypeptidase B (EC 3.4.17.2), obtained from porcine pancreas by Neova Technologies Inc. The food enzyme is intended to be used for hydrolysis of whey proteins employed as ingredients of infant formulae, follow-on formulae and in food for special medical purposes (tube feeding). Based on maximum use levels and the maximum permitted protein content in infant formula, dietary exposure to the food enzyme-total organic solids (TOS) was estimated to be 36 mg TOS/kg body weight (bw) per day for infants. The Panel estimates that this value covers all population groups. In the toxicological evaluation, clinical studies with pharmaceutical preparations containing pancreatic enzymes were considered. Hypersensitivity to the pharmaceuticals was identified as the major side effect. However, the intact enzymes are removed during preparation of food products; therefore, the Panel considers that the likelihood of adverse effects of the intact enzyme to occur is small. Low molecular weight peptides derived from the enzyme are still likely to be present in the protein hydrolysate. The Panel considered that a risk of allergic sensitisation to these peptides after consumption of products prepared by hydrolysis of milk, cannot be excluded in infants, but the likelihood to occur is considered to be low. Based on the origin of the food enzyme from edible parts of animals, the data provided by the applicant, supported by the evaluation of clinical studies with pharmaceutical preparations based on pancreatic enzymes, the Panel concluded that the porcine pancreatic enzymes do not give rise to safety concern under the intended conditions of use. (c) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.Silano, V.; Barat Baviera, JM.; Bolognesi, C.; Cocconcelli, PS.; Crebelli, R.; Gott, DM.; Grob, K.... (2021). Safety evaluation of a food enzyme containing trypsin, chymotrypsin, elastase and carboxypeptidase from porcine pancreas. EFSA Journal. 19(1):1-15. https://doi.org/10.2903/j.efsa.2021.6368S11519

Safety assessment of the substance phosphorous acid, triphenyl ester, polymer with alpha-hydro-omega-hydroxypoly[oxy(methyl-1,2-ethanediyl)], C10-16 alkyl esters (FCM No 1076), for use in food contact materials

[EN] The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) assessed the safety of the substance 'phosphorous acid, triphenyl ester, polymer with alpha-hydro-omega-hydroxypoly[oxy(methyl-1,2-ethanediyl)], C10-16 alkyl esters' obtained by reaction of This food contact material (FCM) substance No 1076 was evaluated by the CEP Panel in 2019 for its use in high impact polystyrene. This opinion deals with the safety assessment of the substance when used as an additive at up to 0.025% w/w in acrylonitrile-butadiene-styrene (ABS) copolymers. The plastic is intended for repeated use in contact with aqueous, acidic, alcoholic and oil-in-water emulsion foods, for long-term storage at room temperature and below. Migration from ABS formulated with the substance at 0.02% w/w was up to 0.002 mg/kg in 10% ethanol, 0.005 mg/kg in 3% acetic acid and 0.027 mg/kg in 50% ethanol. Migration levels into 50% ethanol declined under repeated-use test conditions and this decline was considered to also cover repeated contacts with 10% ethanol and 3% acetic acid simulants. The toxicological data are the same as those submitted by the same applicant in a previous dossier (EFSA-Q-2018-00411). They were reported in the scientific opinion of the CEP Panel in 2019 and the conclusions on toxicity are still valid. Overall, the CEP Panel concluded that the substance phosphorous acid, triphenyl esters, polymer with alpha-hydro-omega-hydroxypoly[oxy(methyl-1,2-ethanediyl)], C10-16 alkyl esters, does not raise a safety concern for the consumer if it is used as an additive at up to 0.025% w/w in ABS materials and articles for single and repeated use in contact with aqueous, acidic, alcoholic and oil-in-water emulsion foods, for long-term storage at room temperature and below, and if its migration does not exceed 0.05 mg/kg food.Lambre, C.; Barat Baviera, JM.; Bolognesi, C.; Chesson, A.; Cocconcelli, PS.; Crebelli, R.; Gott, DM.... (2021). Safety assessment of the substance phosphorous acid, triphenyl ester, polymer with alpha-hydro-omega-hydroxypoly[oxy(methyl-1,2-ethanediyl)], C10-16 alkyl esters (FCM No 1076), for use in food contact materials. EFSA Journal. 19(8):1-8. https://doi.org/10.2903/j.efsa.2021.6786S1819

Safety evaluation of the food enzyme maltogenic alpha-amylase from the genetically modified Saccharomyces cerevisiae strain LALL-MA

[EN] The food enzyme maltogenic alpha-amylase (4-alpha-D-glucan a-maltohydrolase; EC 3.2.1.133) is produced with the genetically modified Saccharomyces cerevisiae strain LALL-MA by Lallemand Baking Solutions. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. The food enzyme is intended to be used in baking processes. Based on the maximum use level recommended for the baking processes and individual data from the EFSA Comprehensive European Food Consumption Database, dietary exposure was estimated to be up to 0.059 mg total organic solids (TOS)/kg body weight per day in European populations. As the production strain of S. cerevisiae meets the requirements for a Qualified Presumption of Safety (QPS) approach, no toxicological data are required. Similarity of the amino acid sequence of the food enzyme to those of known allergens was searched and six matches were found. The Panel considered that under the intended conditions of use, the risk of allergic sensitisation and elicitation reactions by dietary exposure cannot be excluded, but the likelihood for this to occur is considered to be low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use. (C) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.Silano, V.; Barat Baviera, JM.; Bolognesi, C.; Cocconcelli, PS.; Crebelli, R.; Gott, DM.; Grob, K.... (2021). Safety evaluation of the food enzyme maltogenic alpha-amylase from the genetically modified Saccharomyces cerevisiae strain LALL-MA. EFSA Journal. 19(2):1-14. https://doi.org/10.2903/j.efsa.2021.6434S11419