Differential cellular responses in healthy mice and in mice with established airway inflammation when exposed to hematite nanoparticles

Toxicol Appl Pharmacol. 2015 Oct 1;288(1):1-11. doi: 10.1016/j.taap.2015.07.001. Epub 2015 Jul 7.

Abstract

The aim of this study was to investigate the inflammatory and immunological responses in airways and lung-draining lymph nodes (LDLNs), following lung exposure to iron oxide (hematite) nanoparticles (NPs). The responses to the hematite NPs were evaluated in both healthy non-sensitized mice, and in sensitized mice with an established allergic airway disease. The mice were exposed intratracheally to either hematite NPs or to vehicle (PBS) and the cellular responses were evaluated on days 1, 2, and 7, post-exposure. Exposure to hematite NPs increased the numbers of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on days 1 and 2 post-exposure; at these time points the number of lymphocytes was also elevated in the LDLNs. In contrast, exposing sensitized mice to hematite NPs induced a rapid and unspecific cellular reduction in the alveolar space on day 1 post-exposure; a similar decrease of lymphocytes was also observed in the LDLN. The results indicate that cells in the airways and in the LDLN of individuals with established airway inflammation undergo cell death when exposed to hematite NPs. A possible explanation for this toxic response is the extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways. This study demonstrates how sensitized and non-sensitized mice respond differently to hematite NP exposure, and it highlights the importance of including individuals with respiratory disorders when evaluating health effects of inhaled nanomaterials.

Keywords: Hematite; Inflammation; Iron oxide; Nanoparticles; Reactive oxygen species; α-Fe(2)O(3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell Death / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Female
  • Ferric Compounds / toxicity*
  • Inhalation Exposure / adverse effects*
  • Kinetics
  • Lung / drug effects*
  • Lung / immunology
  • Lung / metabolism
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymphocyte Count
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Mice, Inbred BALB C
  • Nanoparticles*
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Ovalbumin
  • Oxidative Stress / drug effects
  • Pneumonia / chemically induced
  • Pneumonia / immunology*
  • Pneumonia / metabolism
  • Reactive Oxygen Species / metabolism
  • Risk Assessment
  • Risk Factors

Substances

  • Cytokines
  • Ferric Compounds
  • Reactive Oxygen Species
  • ferric oxide
  • Ovalbumin