Zinc oxide nanoparticles impair bacterial clearance by macrophages

Nanomedicine (Lond). 2014 Jul;9(9):1327-39. doi: 10.2217/nnm.14.48. Epub 2014 Mar 17.

Abstract

Aim: 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.

Materials & 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.

Conclusion: These results demonstrate that exposure to ZnO-NPs can impair innate immune responses and attenuate macrophage responses to bacterial infection.

Keywords: bronchial alveolar lavage fluid; macrophage; nitric oxide; nontypeable Haemophilus influenzae; zinc oxide nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoalveolar Lavage Fluid / microbiology
  • Cell Line
  • Cytokines / metabolism
  • Haemophilus Infections / immunology
  • Haemophilus Infections / microbiology
  • Haemophilus influenzae / immunology
  • Haemophilus influenzae / pathogenicity
  • Immunity, Innate / drug effects
  • Inflammation Mediators / metabolism
  • Macrophage Activation / drug effects
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / microbiology*
  • Metal Nanoparticles / toxicity*
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Nanomedicine
  • Nitric Oxide / biosynthesis
  • Phagocytosis / drug effects
  • Signal Transduction / drug effects
  • Zinc Oxide / toxicity*

Substances

  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • Nitric Oxide
  • Zinc Oxide