title: A Single Aspiration of Rod-like Carbon Nanotubes Induces Asbestos-like Pulmonary Inflammation Mediated in Part by the IL-1 Receptor.
abstract: Carbon nanotubes (CNT) have been eagerly studied because of their multiple applications in product development and potential risks on health. We investigated the difference of two different CNT and asbestos in inducing proinflammatory reactions in C57BL/6 mice after single pharyngeal aspiration exposure. We used long tangled and long rod-like CNT, as well as crocidolite asbestos at a dose of 10 or 40 µg/mouse. The mice were sacrificed 4 and 16 h or 7, 14, and 28 days after the exposure. To find out the importance of a major inflammatory marker IL-1β in CNT-induced pulmonary inflammation, we used etanercept and anakinra as antagonists as well as Interleukin 1 (IL-1) receptor (IL-1R-/-) mice. The results showed that rod-like CNT, and asbestos in lesser extent, induced strong pulmonary neutrophilia accompanied by the proinflammatory cytokines and chemokines 16 h after the exposure. Seven days after the exposure, neutrophilia had essentially disappeared but strong pulmonary eosinophilia peaked in rod-like CNT and asbestos-exposed groups. After 28 days, pulmonary granulomas, goblet cell hyperplasia, and Charcot-Leyden-like crystals containing acidophilic macrophages were observed especially in rod-like CNT-exposed mice. IL-1R-/- mice and antagonists-treated mice exhibited a significant decrease in neutrophilia and messenger ribonucleic acid (mRNA) levels of proinflammatory cytokines at 16 h. However, rod-like CNT-induced Th2-type inflammation evidenced by the expression of IL-13 and mucus production was unaffected in IL-1R-/- mice at 28 days. This study provides knowledge about the pulmonary effects induced by a single exposure to the CNT and contributes to hazard assessment of carbon nanomaterials on airway exposure.
authors.affiliation: *Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki 00250, Finland;
authors.forename: Elina M
authors.initials: EM
authors.lastname: Rydman
authors.affiliation: *Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki 00250, Finland;
authors.forename: Marit
authors.initials: M
authors.lastname: Ilves
authors.affiliation: *Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki 00250, Finland;
authors.forename: Esa
authors.initials: E
authors.lastname: Vanhala
authors.affiliation: Department of Materials Science, Tampere University of Technology, Tampere 33101, Finland; and.
authors.forename: Minnamari
authors.initials: M
authors.lastname: Vippola
authors.affiliation: *Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki 00250, Finland;
authors.forename: Maili
authors.initials: M
authors.lastname: Lehto
authors.affiliation: *Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki 00250, Finland;
authors.forename: Pia A S
authors.initials: PA
authors.lastname: Kinaret
authors.affiliation: *Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki 00250, Finland;
authors.forename: Lea
authors.initials: L
authors.lastname: Pylkkänen
authors.affiliation: Department of Environmental Science, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Happo
authors.affiliation: Department of Environmental Science, University of Eastern Finland, Kuopio, Finland.
authors.forename: Maija-Riitta
authors.initials: MR
authors.lastname: Hirvonen
authors.affiliation: *Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki 00250, Finland;
authors.forename: Dario
authors.initials: D
authors.lastname: Greco
authors.affiliation: *Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki 00250, Finland;
authors.forename: Kai
authors.initials: K
authors.lastname: Savolainen
authors.affiliation: *Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki 00250, Finland;
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.affiliation: *Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki 00250, Finland; harri.alenius@ttl.fi.
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
mesh_terms: D000818:Animals; D001194:Asbestos / Q000633:toxicity*; D017638:Asbestos, Crocidolite / Q000633:toxicity; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D018925:Chemokines; D016207:Cytokines; D037742:Nanotubes, Carbon; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D017638:Asbestos, Crocidolite; D001194:Asbestos
keywords: Charcot-Leyden-like crystals; IL-1β; Th2; asbestos; multiwalled carbon nanotubes