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Preventing carbon nanoparticle-induced lung inflammation reduces antigen-specific sensitization and subsequent allergic reactions in a mouse model.

Kroker M, Sydlik U, Autengruber A, Cavelius C, Weighardt H, Kraegeloh A, Unfried K - Part Fibre Toxicol (2015)

Bottom Line: The presence of ectoine during the sensitization significantly reduced these parameters.The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles.Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization.

View Article: PubMed Central - PubMed

Affiliation: IUF - Leibniz Institut für Umweltmedizinische Forschung, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany.

ABSTRACT

Background: Exposure of the airways to carbonaceous nanoparticles can contribute to the development of immune diseases both via the aggravation of the allergic immune response in sensitized individuals and by adjuvant mechanisms during the sensitization against allergens. The cellular and molecular mechanisms involved in these adverse pathways are not completely understood. We recently described that the reduction of carbon nanoparticle-induced lung inflammation by the application of the compatible solute ectoine reduced the aggravation of the allergic response in an animal system. In the current study we investigated the influence of carbon nanoparticles on the sensitization of animals to ovalbumin via the airways. Ectoine was used as a preventive strategy against nanoparticle-induced neutrophilic lung inflammation.

Methods: Balb/c mice were repetitively exposed to the antigen ovalbumin after induction of airway inflammation by carbon nanoparticles, either in the presence or in the absence of ectoine. Allergic sensitization was monitored by measurement of immunoglobulin levels and immune responses in lung and lung draining lymph nodes after challenge. Furthermore the role of dendritic cells in the effect of carbon nanoparticles was studied in vivo in the lymph nodes but also in vitro using bone marrow derived dendritic cells.

Results: Animals exposed to antigen in the presence of carbon nanoparticles showed increased effects with respect to ovalbumin sensitization, to the allergic airway inflammation after challenge, and to the specific TH2 response in the lymph nodes. The presence of ectoine during the sensitization significantly reduced these parameters. The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles. In vitro assays indicate that the direct interaction of the particles with dendritic cells is not able to trigger CCR7 expression, while this endpoint is achieved by lung lavage fluid from nanoparticle-exposed animals.

Conclusions: Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization.

No MeSH data available.


Related in: MedlinePlus

Changes in lymph node responses after challenge. Lymph nodes from the animals (Fig. 2) were analysed for adaptive immune responses. a Total cell numbers in peribronchial lymph nodes (representative plots and means, SEM). b IL-4 release in re-stimulated lymph node cells. c IL-13 release in re-stimulated lymph node cells. *p < 0.05, Mann Whitney U-test
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Fig3: Changes in lymph node responses after challenge. Lymph nodes from the animals (Fig. 2) were analysed for adaptive immune responses. a Total cell numbers in peribronchial lymph nodes (representative plots and means, SEM). b IL-4 release in re-stimulated lymph node cells. c IL-13 release in re-stimulated lymph node cells. *p < 0.05, Mann Whitney U-test

Mentions: In order to verify the effect of CNP on the sensitization against OVA and to further investigate the possible effects of ectoine on this process, we studied the adaptive immune reactions in the peribronchial lymph nodes of the animals at day 35 by flow cytometry (Fig. 3a). Total cell numbers appeared to reflect the sensitization status of the animals. A significant increase in all tested cell types (B cells, CD8+ T cells, and CD4+ T cells) was observed in animals which were sensitized in the presence of CNP. Numbers of all cell types were lower in the animals in which ectoine was present in the initial experimental phase. As an additional readout for differences in the immune status of the animals, cultured lymph node cells were re-stimulated with OVA and the TH2 cytokines IL-4 (Fig. 3b) and IL-13 (Fig. 3c) were determined in the supernatants. Both cytokines were significantly elevated only in cell cultures from animals sensitized in the presence of CNP. A statistically significant reduction was observed for the IL-13 release in the samples from CNP plus ectoine animals, whereas IL-4 levels were not altered significantly by ectoine.Fig. 3


Preventing carbon nanoparticle-induced lung inflammation reduces antigen-specific sensitization and subsequent allergic reactions in a mouse model.

Kroker M, Sydlik U, Autengruber A, Cavelius C, Weighardt H, Kraegeloh A, Unfried K - Part Fibre Toxicol (2015)

Changes in lymph node responses after challenge. Lymph nodes from the animals (Fig. 2) were analysed for adaptive immune responses. a Total cell numbers in peribronchial lymph nodes (representative plots and means, SEM). b IL-4 release in re-stimulated lymph node cells. c IL-13 release in re-stimulated lymph node cells. *p < 0.05, Mann Whitney U-test
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4491258&req=5

Fig3: Changes in lymph node responses after challenge. Lymph nodes from the animals (Fig. 2) were analysed for adaptive immune responses. a Total cell numbers in peribronchial lymph nodes (representative plots and means, SEM). b IL-4 release in re-stimulated lymph node cells. c IL-13 release in re-stimulated lymph node cells. *p < 0.05, Mann Whitney U-test
Mentions: In order to verify the effect of CNP on the sensitization against OVA and to further investigate the possible effects of ectoine on this process, we studied the adaptive immune reactions in the peribronchial lymph nodes of the animals at day 35 by flow cytometry (Fig. 3a). Total cell numbers appeared to reflect the sensitization status of the animals. A significant increase in all tested cell types (B cells, CD8+ T cells, and CD4+ T cells) was observed in animals which were sensitized in the presence of CNP. Numbers of all cell types were lower in the animals in which ectoine was present in the initial experimental phase. As an additional readout for differences in the immune status of the animals, cultured lymph node cells were re-stimulated with OVA and the TH2 cytokines IL-4 (Fig. 3b) and IL-13 (Fig. 3c) were determined in the supernatants. Both cytokines were significantly elevated only in cell cultures from animals sensitized in the presence of CNP. A statistically significant reduction was observed for the IL-13 release in the samples from CNP plus ectoine animals, whereas IL-4 levels were not altered significantly by ectoine.Fig. 3

Bottom Line: The presence of ectoine during the sensitization significantly reduced these parameters.The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles.Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization.

View Article: PubMed Central - PubMed

Affiliation: IUF - Leibniz Institut für Umweltmedizinische Forschung, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany.

ABSTRACT

Background: Exposure of the airways to carbonaceous nanoparticles can contribute to the development of immune diseases both via the aggravation of the allergic immune response in sensitized individuals and by adjuvant mechanisms during the sensitization against allergens. The cellular and molecular mechanisms involved in these adverse pathways are not completely understood. We recently described that the reduction of carbon nanoparticle-induced lung inflammation by the application of the compatible solute ectoine reduced the aggravation of the allergic response in an animal system. In the current study we investigated the influence of carbon nanoparticles on the sensitization of animals to ovalbumin via the airways. Ectoine was used as a preventive strategy against nanoparticle-induced neutrophilic lung inflammation.

Methods: Balb/c mice were repetitively exposed to the antigen ovalbumin after induction of airway inflammation by carbon nanoparticles, either in the presence or in the absence of ectoine. Allergic sensitization was monitored by measurement of immunoglobulin levels and immune responses in lung and lung draining lymph nodes after challenge. Furthermore the role of dendritic cells in the effect of carbon nanoparticles was studied in vivo in the lymph nodes but also in vitro using bone marrow derived dendritic cells.

Results: Animals exposed to antigen in the presence of carbon nanoparticles showed increased effects with respect to ovalbumin sensitization, to the allergic airway inflammation after challenge, and to the specific TH2 response in the lymph nodes. The presence of ectoine during the sensitization significantly reduced these parameters. The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles. In vitro assays indicate that the direct interaction of the particles with dendritic cells is not able to trigger CCR7 expression, while this endpoint is achieved by lung lavage fluid from nanoparticle-exposed animals.

Conclusions: Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization.

No MeSH data available.


Related in: MedlinePlus