title: Comparison of pulmonary inflammatory responses following intratracheal instillation and inhalation of nanoparticles.
abstract: In order to examine whether intratracheal instillation studies can be useful for determining the harmful effect of nanoparticles, we performed inhalation and intratracheal instillation studies using samples of the same nanoparticles. Nickel oxide nanoparticles (NiO) and titanium dioxide nanoparticles (TiO2) were used as chemicals with high and low toxicities, respectively. In the intratracheal instillation study, rats were exposed to 0.2 or 1 mg of NiO or TiO2. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the single intratracheal instillation. In the inhalation study, rats were exposed to inhaled NiO or TiO2 (1.65, 1.84 mg/m(3), respectively) for 4 weeks. The same endpoints were examined from 3 days to 3 months after the end of exposure. Inhalation of NiO induced an increase in the number of neutrophils in BALF and concentrations of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and heme oxygenase (HO)-1. Intratracheal instillation of NiO induced persistent inflammation and upregulation of these cytokines was observed in the rats. However, inhalation of TiO2 did not induce pulmonary inflammation, and intratracheal instillation of TiO2 transiently induced an increase in the number of neutrophils in BALF and the concentrations of CINC-1, CINC-2 and HO-1. Taken together, a difference in pulmonary inflammation was observed between the high and low toxicity nanomaterials in the intratracheal instillation studies, as in the inhalation studies, suggesting that intratracheal instillation studies may be useful for ranking the harmful effects of nanoparticles.
authors.affiliation: a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
authors.affiliation: a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.affiliation: a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yoshiura
authors.affiliation: a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .
authors.forename: Taisuke
authors.initials: T
authors.lastname: Tomonaga
authors.affiliation: a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .
authors.forename: Byeong-Woo
authors.initials: BW
authors.lastname: Lee
authors.affiliation: a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .
authors.forename: Takami
authors.initials: T
authors.lastname: Okada
authors.affiliation: a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .
authors.forename: Takako
authors.initials: T
authors.lastname: Oyabu
authors.affiliation: a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Myojo
authors.affiliation: a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kawai
authors.affiliation: a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yatera
authors.affiliation: b Hiroshima University , Higashi-Hiroshima , Japan .
authors.forename: Manabu
authors.initials: M
authors.lastname: Shimada
authors.affiliation: b Hiroshima University , Higashi-Hiroshima , Japan .
authors.forename: Masaru
authors.initials: M
authors.lastname: Kubo
authors.affiliation: c National Institute of Advanced Industrial Science and Technology , Tsukuba , Japan .
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: d Division of Research and Examination , National Sanatorium Hoshizuka Keiaien , Kanoya , Japan , and.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kitajima
authors.affiliation: e Laboratory of Vaccine Science , WPI Immunology Frontier Research Center, Osaka University , Osaka , Japan.
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.affiliation: a University of Occupational and Environmental Health , Kitakyushu , Fukuoka , Japan .|c National Institute of Advanced Industrial Science and Technology , Tsukuba , Japan .
authors.forename: Masanori
authors.initials: M
authors.lastname: Horie
authors.affiliation: c National Institute of Advanced Industrial Science and Technology , Tsukuba , Japan .
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: c National Institute of Advanced Industrial Science and Technology , Tsukuba , Japan .
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000276:immunology; D007322:Instillation, Drug; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects; D009532:Nickel / Q000008:administration & dosage / Q000633:toxicity; D011014:Pneumonia / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D016207:Cytokines; C009495:titanium dioxide; D009532:Nickel; C028007:nickel monoxide; D014025:Titanium
keywords: Inflammation; inhalation; intratracheal instillation; nanoparticle; rat