title: Differential pulmonary effects of CoO and La2O3 metal oxide nanoparticle responses during aerosolized inhalation in mice.
abstract: Although classified as metal oxides, cobalt monoxide (CoO) and lanthanum oxide (La2O3) nanoparticles, as representative transition and rare earth oxides, exhibit distinct material properties that may result in different hazardous potential in the lung. The current study was undertaken to compare the pulmonary effects of aerosolized whole body inhalation of these nanoparticles in mice.
  
  
  
  Mice were exposed to filtered air (control) and 10 or 30 mg/m(3) of each particle type for 4 days and then examined at 1 h, 1, 7 and 56 days post-exposure. The whole lung burden 1 h after the 4 day inhalation of CoO nanoparticles was 25 % of that for La2O3 nanoparticles. At 56 days post exposure, < 1 % of CoO nanoparticles remained in the lungs; however, 22-50 % of the La2O3 nanoparticles lung burden 1 h post exposure was retained at 56 days post exposure for low and high exposures. Significant accumulation of La2O3 nanoparticles in the tracheobronchial lymph nodes was noted at 56 days post exposure. When exposed to phagolysosomal simulated fluid, La nanoparticles formed urchin-shaped LaPO4 structures, suggesting that retention of this rare earth oxide nanoparticle may be due to complexation of cellular phosphates within lysosomes. CoO nanoparticles caused greater lactate dehydrogenase release in the bronchoalveolar fluid (BALF) compared to La2O3 nanoparticles at 1 day post exposure, while BAL cell differentials indicate that La2O3 nanoparticles generated more inflammatory cell infiltration at all doses and exposure points. Histopathological analysis showed acute inflammatory changes at 1 day after inhalation of either CoO or La2O3 nanoparticles. Only the 30 mg/m(3) La2O3 nanoparticles exposure caused chronic inflammatory changes and minimal fibrosis at day 56 post exposure. This is in agreement with activation of the NRLP3 inflammasome after in vitro exposure of differentiated THP-1 macrophages to La2O3 but not after CoO nanoparticles exposure.
  
  
  
  Taken together, the inhalation studies confirmed the trend of our previous sub-acute aspiration study, which reported that CoO nanoparticles induced more acute pulmonary toxicity, while La2O3 nanoparticles caused chronic inflammatory changes and minimal fibrosis.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Sisler
authors.affiliation: Division of NanoMedicine, Department of Medicine, University of California, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA.|Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, CA, 90095, USA.|School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China.
authors.forename: Ruibin
authors.initials: R
authors.lastname: Li
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Walter
authors.initials: W
authors.lastname: McKinney
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Mercer
authors.affiliation: California NanoSystems Institute, University of California, 570 Westwood Plaza, Los Angeles, CA, 90095, USA.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Division of NanoMedicine, Department of Medicine, University of California, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA.|Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, CA, 90095, USA.|California NanoSystems Institute, University of California, 570 Westwood Plaza, Los Angeles, CA, 90095, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.affiliation: California NanoSystems Institute, University of California, 570 Westwood Plaza, Los Angeles, CA, 90095, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Justine
authors.initials: J
authors.lastname: Shaffer
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Marlene
authors.initials: M
authors.lastname: Orandle
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Mihalchik
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Battelli
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Bean T
authors.initials: BT
authors.lastname: Chen
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wolfarth
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Andrew
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Schwegler-Berry
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA.
authors.forename: Dale W
authors.initials: DW
authors.lastname: Porter
authors.affiliation: Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.affiliation: Division of NanoMedicine, Department of Medicine, University of California, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA.|Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, CA, 90095, USA.|California NanoSystems Institute, University of California, 570 Westwood Plaza, Los Angeles, CA, 90095, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Nel
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA. yaq2@cdc.gov.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
mesh_terms: D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D003035:Cobalt / Q000493:pharmacokinetics / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D019570:Inhalation Exposure; D007811:Lanthanum / Q000493:pharmacokinetics / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D010087:Oxides / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D000336:Aerosols; D016207:Cytokines; D010087:Oxides; D003035:Cobalt; C103829:lanthanum oxide; D007811:Lanthanum; C060728:cobalt oxide
keywords: In vivo; Metal oxides; Mouse; Nanoparticles; Pulmonary response