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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

Ectoine application reduces neutrophilic lung inflammation induced by CNP in Balb/c mice. a Experimental design, animals (n = 5) were exposed to PBS (control), 2.5 mg/kg CNP, or 2.5 mg/kg CNP with 1 mM ectoine (E) and subsequently sacrificed at the indicate time points. b Differential cell numbers in BAL (means, SEM). c CXCL1 levels in BAL. * significant differences were observed in total cell numbers, neutrophil numbers and CXCL1 levels (p < 0.05, Mann Whitney U-test)
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Fig1: Ectoine application reduces neutrophilic lung inflammation induced by CNP in Balb/c mice. a Experimental design, animals (n = 5) were exposed to PBS (control), 2.5 mg/kg CNP, or 2.5 mg/kg CNP with 1 mM ectoine (E) and subsequently sacrificed at the indicate time points. b Differential cell numbers in BAL (means, SEM). c CXCL1 levels in BAL. * significant differences were observed in total cell numbers, neutrophil numbers and CXCL1 levels (p < 0.05, Mann Whitney U-test)

Mentions: In a pilot animal study, the effect of ectoine on the lung inflammation induced by the pharyngeal aspiration of 2.5 mg/kg CNP was investigated after 12, 24, and 48 h (Fig. 1a). A mild inflammatory increase in total cells numbers and specifically in neutrophils was observed 12 h after single application of CNP in the broncho-alveolar lavage (BAL) as compared to BAL of control mice (Fig. 1b). Following the kinetics of the lung inflammation, at later time points decreasing numbers of neutrophils were observed, while the number of clearing macrophages was increased. Accordingly, the application of 1 mM ectoine together with the particles led to a reduction of total cell numbers due to the significantly lower neutrophil numbers. Ectoine had no significant effect on the number of macrophages at all time points. This effect was nicely reflected at the level of the neutrophil recruiting chemokine CXCL1 (homologue to human IL-8). In earlier studies we demonstrated that the effect on the reduction of neutrophilic lung inflammation is not due to changes in particle properties but is caused by the effect of ectoine on membrane dependent signalling processes both in lung epithelial cells and in neutrophils [17]. As previously published, ectoine also reduced the amount of cytokines like IL-5 and IL-6 in BAL of exposed mice after 12 h [24]. The data demonstrate that neutrophilic lung inflammation induced by pharyngeal aspiration of CNP can be modulated by the application of ectoine. This system enabled us to study the influence of the inflammatory reaction on allergic sensitization via the lower airways.Fig. 1


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)

Ectoine application reduces neutrophilic lung inflammation induced by CNP in Balb/c mice. a Experimental design, animals (n = 5) were exposed to PBS (control), 2.5 mg/kg CNP, or 2.5 mg/kg CNP with 1 mM ectoine (E) and subsequently sacrificed at the indicate time points. b Differential cell numbers in BAL (means, SEM). c CXCL1 levels in BAL. * significant differences were observed in total cell numbers, neutrophil numbers and CXCL1 levels (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

Fig1: Ectoine application reduces neutrophilic lung inflammation induced by CNP in Balb/c mice. a Experimental design, animals (n = 5) were exposed to PBS (control), 2.5 mg/kg CNP, or 2.5 mg/kg CNP with 1 mM ectoine (E) and subsequently sacrificed at the indicate time points. b Differential cell numbers in BAL (means, SEM). c CXCL1 levels in BAL. * significant differences were observed in total cell numbers, neutrophil numbers and CXCL1 levels (p < 0.05, Mann Whitney U-test)
Mentions: In a pilot animal study, the effect of ectoine on the lung inflammation induced by the pharyngeal aspiration of 2.5 mg/kg CNP was investigated after 12, 24, and 48 h (Fig. 1a). A mild inflammatory increase in total cells numbers and specifically in neutrophils was observed 12 h after single application of CNP in the broncho-alveolar lavage (BAL) as compared to BAL of control mice (Fig. 1b). Following the kinetics of the lung inflammation, at later time points decreasing numbers of neutrophils were observed, while the number of clearing macrophages was increased. Accordingly, the application of 1 mM ectoine together with the particles led to a reduction of total cell numbers due to the significantly lower neutrophil numbers. Ectoine had no significant effect on the number of macrophages at all time points. This effect was nicely reflected at the level of the neutrophil recruiting chemokine CXCL1 (homologue to human IL-8). In earlier studies we demonstrated that the effect on the reduction of neutrophilic lung inflammation is not due to changes in particle properties but is caused by the effect of ectoine on membrane dependent signalling processes both in lung epithelial cells and in neutrophils [17]. As previously published, ectoine also reduced the amount of cytokines like IL-5 and IL-6 in BAL of exposed mice after 12 h [24]. The data demonstrate that neutrophilic lung inflammation induced by pharyngeal aspiration of CNP can be modulated by the application of ectoine. This system enabled us to study the influence of the inflammatory reaction on allergic sensitization via the lower airways.Fig. 1

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