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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

Effects of CNP and lavage fluid on bone marrow derived dendritic cells. Dendritic cells derived from Balb/c mice (n = 7) were exposed to the indicated doses of CNP (a) or lavage fluid (b) from exposed animals. c Representative histograms determining CCR7+ cells. *significantly different from PBS alone, # significantly different from cells treated with BAL from CNP-exposed animals. (p < 0.05, ANOVA with post hoc testing)
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Fig5: Effects of CNP and lavage fluid on bone marrow derived dendritic cells. Dendritic cells derived from Balb/c mice (n = 7) were exposed to the indicated doses of CNP (a) or lavage fluid (b) from exposed animals. c Representative histograms determining CCR7+ cells. *significantly different from PBS alone, # significantly different from cells treated with BAL from CNP-exposed animals. (p < 0.05, ANOVA with post hoc testing)

Mentions: To address the question whether these effects are mediated by the particles themselves or rather by factors released during airway inflammation, bone marrow derived dendritic cells were exposed in vitro to CNP and to cell free BAL fluids from exposed and control animals (Fig. 5). The cells were tested for the expression of the chemokine receptor CCR7 which is crucial for migration of antigen presenting cells from the periphery to draining lymph nodes [28]. As expected, lipopolysaccharide (LPS) as a positive control enhanced the number of CCR7 positive dendritic cells. This effect was not influenced in the presence of ectoine. Incubating the cells with different doses of CNP suspensions did not lead to an increase of CCR7 positive cells (Fig. 5a). At least under these conditions the nanoparticles had no effect on the dendritic cells. However, treating the cells with lavage fluids, devoid of cells and particles, from animals which had been exposed to CNP for 12 h revealed very clear results (Fig. 5b). A significant increase in CCR7 positive cells was observed after treatment with the lavage from CNP alone treated animals. This response was significantly lower in samples incubated with lavage from CNP plus ectoine-treated animals. The induction of CCR7, however, was not significantly reduced when ectoine was added to the dendritic cell cultures in vitro as an intervention strategy against the effects of lavage fluid from CNP-alone animals. Other studies have shown that CNP in contrast to ambient particles do not induce the activation of dendritic cells [29]. Similar results were obtained when we tested bone marrow derived dendritic cells for the expression of CD86 after treatment with CNP and lavage fluid (data not shown).Fig. 5


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)

Effects of CNP and lavage fluid on bone marrow derived dendritic cells. Dendritic cells derived from Balb/c mice (n = 7) were exposed to the indicated doses of CNP (a) or lavage fluid (b) from exposed animals. c Representative histograms determining CCR7+ cells. *significantly different from PBS alone, # significantly different from cells treated with BAL from CNP-exposed animals. (p < 0.05, ANOVA with post hoc testing)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Effects of CNP and lavage fluid on bone marrow derived dendritic cells. Dendritic cells derived from Balb/c mice (n = 7) were exposed to the indicated doses of CNP (a) or lavage fluid (b) from exposed animals. c Representative histograms determining CCR7+ cells. *significantly different from PBS alone, # significantly different from cells treated with BAL from CNP-exposed animals. (p < 0.05, ANOVA with post hoc testing)
Mentions: To address the question whether these effects are mediated by the particles themselves or rather by factors released during airway inflammation, bone marrow derived dendritic cells were exposed in vitro to CNP and to cell free BAL fluids from exposed and control animals (Fig. 5). The cells were tested for the expression of the chemokine receptor CCR7 which is crucial for migration of antigen presenting cells from the periphery to draining lymph nodes [28]. As expected, lipopolysaccharide (LPS) as a positive control enhanced the number of CCR7 positive dendritic cells. This effect was not influenced in the presence of ectoine. Incubating the cells with different doses of CNP suspensions did not lead to an increase of CCR7 positive cells (Fig. 5a). At least under these conditions the nanoparticles had no effect on the dendritic cells. However, treating the cells with lavage fluids, devoid of cells and particles, from animals which had been exposed to CNP for 12 h revealed very clear results (Fig. 5b). A significant increase in CCR7 positive cells was observed after treatment with the lavage from CNP alone treated animals. This response was significantly lower in samples incubated with lavage from CNP plus ectoine-treated animals. The induction of CCR7, however, was not significantly reduced when ectoine was added to the dendritic cell cultures in vitro as an intervention strategy against the effects of lavage fluid from CNP-alone animals. Other studies have shown that CNP in contrast to ambient particles do not induce the activation of dendritic cells [29]. Similar results were obtained when we tested bone marrow derived dendritic cells for the expression of CD86 after treatment with CNP and lavage fluid (data not shown).Fig. 5

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