title: Zinc oxide nanoparticles impair bacterial clearance by macrophages.
abstract: OBJECTIVE
  The extensive development of nanoparticles (NPs) and their widespread employment in daily life have led to an increase in environmental concentrations of substances that may pose a biohazard to humans. The aim of this work was to examine the effects of zinc oxide nanoparticles (ZnO-NPs) on the host's pulmonary immune system response to nontypeable Haemophilus influenzae (NTHi) infection.
  
  
  METHODS
  A murine infection model was employed to assess pulmonary inflammation and bacterial clearance in response to exposure to ZnO-NPs. The molecular mechanisms underlying ZnO-NP-impaired macrophage activation were investigated.
  
  
  RESULTS
  Treatment with ZnO-NPs impaired macrophage activation, leading to a delay in NTHi clearance in the bronchial alveolar lavage fluids and lungs. Exposure to ZnO-NPs followed by NTHi challenge decreased levels of nitric oxide compared with NTHi infection alone. The effects of ZnO-NPs involved downregulation of NTHi-activated expression of inducible nitric oxide synthase and the translocation of active NF-kB into the nucleus.
  
  
  CONCLUSIONS
  These results demonstrate that exposure to ZnO-NPs can impair innate immune responses and attenuate macrophage responses to bacterial infection.
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chia-Der
authors.initials: CD
authors.lastname: Lin
authors.forename: Yu-Yi
authors.initials: YY
authors.lastname: Kou
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Liao
authors.forename: Ching-Hao
authors.initials: CH
authors.lastname: Li
authors.forename: Shiao-Ping
authors.initials: SP
authors.lastname: Huang
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Cheng
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Liao
authors.forename: Hao-Xiang
authors.initials: HX
authors.lastname: Chen
authors.forename: Pei-Ling
authors.initials: PL
authors.lastname: Wu
authors.forename: Jaw-Jou
authors.initials: JJ
authors.lastname: Kang
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Lee
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D006192:Haemophilus Infections / Q000276:immunology / Q000382:microbiology; D006193:Haemophilus influenzae / Q000276:immunology / Q000472:pathogenicity; D007113:Immunity, Innate / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology*; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D050997:Nanomedicine; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D009569:Nitric Oxide; D015034:Zinc Oxide
keywords: bronchial alveolar lavage fluid; macrophage; nitric oxide; nontypeable Haemophilus influenzae; zinc oxide nanoparticles