title: Preventing carbon nanoparticle-induced lung inflammation reduces antigen-specific sensitization and subsequent allergic reactions in a mouse model.
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.
authors.affiliation: IUF - Leibniz Institut für Umweltmedizinische Forschung, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kroker
authors.affiliation: IUF - Leibniz Institut für Umweltmedizinische Forschung, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sydlik
authors.affiliation: IUF - Leibniz Institut für Umweltmedizinische Forschung, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Autengruber
authors.affiliation: INM - Leibniz Institut für Neue Materialien, Saarbrücken, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Cavelius
authors.affiliation: LIMES Institut, Universität Bonn, Bonn, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Weighardt
authors.affiliation: INM - Leibniz Institut für Neue Materialien, Saarbrücken, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Kraegeloh
authors.affiliation: IUF - Leibniz Institut für Umweltmedizinische Forschung, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany. Klaus.Unfried@uni-duesseldorf.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Unfried
mesh_terms: D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002244:Carbon / Q000633:toxicity*; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D054400:Receptors, CCR7 / Q000276:immunology / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000599:Amino Acids, Diamino; D000893:Anti-Inflammatory Agents; C515371:Ccr7 protein, mouse; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D018793:Interleukin-13; D054400:Receptors, CCR7; D015847:Interleukin-4; D002244:Carbon; C045628:ectoine; D010047:Ovalbumin