title: Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL/6 mice.
abstract: BACKGROUND
  Multi-walled carbon nanotubes (MWCNTs) are widely used in many disciplines due to their unique physical and chemical properties. Therefore, some concerns about the possible human health and environmental impacts of manufactured MWCNTs are rising. We hypothesized that instillation of MWCNTs impairs pulmonary function in C57BL/6 mice due to development of lung inflammation and fibrosis.
  
  
  METHODS
  MWCNTs were administered to C57BL/6 mice by oropharyngeal aspiration (1, 2, and 4 mg/kg) and we assessed lung inflammation and fibrosis by inflammatory cell infiltration, collagen content, and histological assessment. Pulmonary function was assessed using a FlexiVent system and levels of Ccl3, Ccl11, Mmp13 and IL-33 were measured by RT-PCR and ELISA.
  
  
  RESULTS
  Mice administered MWCNTs exhibited increased inflammatory cell infiltration, collagen deposition and granuloma formation in lung tissue, which correlated with impaired pulmonary function as assessed by increased resistance, tissue damping, and decreased lung compliance. Pulmonary exposure to MWCNTs induced an inflammatory signature marked by cytokine (IL-33), chemokine (Ccl3 and Ccl11), and protease production (Mmp13) that promoted the inflammatory and fibrotic changes observed within the lung.
  
  
  CONCLUSIONS
  These results further highlight the potential adverse health effects that may occur following MWCNT exposure and therefore we suggest these materials may pose a significant risk leading to impaired lung function following environmental and occupational exposures.
authors.affiliation: Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA. wangx@ecu.edu
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Wang
authors.forename: Pranita
authors.initials: P
authors.lastname: Katwa
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Podila
authors.forename: Pengyu
authors.initials: P
authors.lastname: Chen
authors.forename: Pu Chun
authors.initials: PC
authors.lastname: Ke
authors.forename: Apparao M
authors.initials: AM
authors.lastname: Rao
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Walters
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wingard
authors.forename: Jared M
authors.initials: JM
authors.lastname: Brown
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure / Q000009:adverse effects*; D007322:Instillation, Drug; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D012129:Respiratory Function Tests; D013499:Surface Properties
chemical_list: D016207:Cytokines; D037742:Nanotubes, Carbon; D003094:Collagen