title: Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation.
abstract: BACKGROUND
  Carbon nanotubes (CNT) represent a great promise for technological and industrial development but serious concerns on their health effects have also emerged. Rod-shaped CNT are, in fact, able to induce asbestos-like pathogenicity in mice including granuloma formation in abdominal cavity and sub-pleural fibrosis. Exposure to CNT, especially in the occupational context, happens mainly by inhalation. However, little is known about the possible effects of CNT on pulmonary allergic diseases, such as asthma.
  
  
  METHODS
  We exposed mice by inhalation to two types of multi-walled CNT, rigid rod-like and flexible tangled CNT, for four hours a day once or on four consecutive days. Early events were monitored immediately and 24 hours after the single inhalation exposure and the four day exposure mimicked an occupational work week. Mast cell deficient mice were used to evaluate the role of mast cells in the occurring inflammation.
  
  
  RESULTS
  Here we show that even a short-term inhalation of the rod-like CNT induces novel innate immunity-mediated allergic-like airway inflammation in healthy mice. Marked eosinophilia was accompanied by mucus hypersecretion, AHR and the expression of Th2-type cytokines. Exploration of the early events by transcriptomics analysis reveals that a single 4-h exposure to rod-shaped CNT, but not to tangled CNT, causes a radical up-regulation of genes involved in innate immunity and cytokine/chemokine pathways. Mast cells were found to partially regulate the inflammation caused by rod-like CNT, but also alveaolar macrophages play an important role in the early stages.
  
  
  CONCLUSIONS
  These observations emphasize the diverse abilities of CNT to impact the immune system, and they should be taken into account for hazard assessment.
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. elina.rydman@ttl.fi.
authors.forename: Elina M
authors.initials: EM
authors.lastname: Rydman
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. marit.ilves@ttl.fi.
authors.forename: Marit
authors.initials: M
authors.lastname: Ilves
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. joonas.koivisto@ttl.fi.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Koivisto
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. pia.kinaret@ttl.fi.
authors.forename: Pia A S
authors.initials: PA
authors.lastname: Kinaret
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. vittorio.fortino@ttl.fi.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Fortino
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. terhi.savinko@ttl.fi.
authors.forename: Terhi S
authors.initials: TS
authors.lastname: Savinko
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. maili.lehto@ttl.fi.
authors.forename: Maili T
authors.initials: MT
authors.lastname: Lehto
authors.affiliation: Pulmonary Division, Department of Medicine, University of Helsinki, Helsinki, Finland. ville.pulkkinen@helsinki.fi.
authors.forename: Ville
authors.initials: V
authors.lastname: Pulkkinen
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. minnamari.vippola@tut.fi.|Department of Materials Science, Tampere University of Technology, Tampere, Finland. minnamari.vippola@tut.fi.
authors.forename: Minnamari
authors.initials: M
authors.lastname: Vippola
authors.affiliation: Department of Physics, University of Helsinki, Helsinki, Finland. kaarle.hameri@helsinki.fi.
authors.forename: Kaarle J
authors.initials: KJ
authors.lastname: Hämeri
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. sampsa.matikainen@ttl.fi.
authors.forename: Sampsa
authors.initials: S
authors.lastname: Matikainen
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. henrik.wolff@ttl.fi.
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. kai.savolainen@ttl.fi.
authors.forename: Kai M
authors.initials: KM
authors.lastname: Savolainen
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. dario.greco@ttl.fi.
authors.forename: Dario
authors.initials: D
authors.lastname: Greco
authors.affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. harri.alenius@ttl.fi.
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
mesh_terms: D000336:Aerosols; D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D016207:Cytokines / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D004802:Eosinophilia / Q000209:etiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D019570:Inhalation Exposure / Q000009:adverse effects*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D012130:Respiratory Hypersensitivity / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012137:Respiratory System / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000336:Aerosols; D000393:Air Pollutants; D016207:Cytokines; D037742:Nanotubes, Carbon