Development of Combining of Human Bronchial Mucosa Models with XposeALI® for Exposure of Air Pollution Nanoparticles

PLoS One. 2017 Jan 20;12(1):e0170428. doi: 10.1371/journal.pone.0170428. eCollection 2017.

Abstract

Background: Exposure to agents via inhalation is of great concerns both in workplace environment and in the daily contact with particles in the ambient air. Reliable human airway exposure systems will most likely replace animal experiment in future toxicity assessment studies of inhaled agents.

Methods: In this study, we successfully established a combination of an exposure system (XposeALI) with 3D models mimicking both healthy and chronic bronchitis-like mucosa by co-culturing human primary bronchial epithelial cells (PBEC) and fibroblast at air-liquid interface (ALI). Light-, confocal microscopy, scanning- and transmission electron microscopy, transepithelial electrical resistance (TEER) measurement and RT-PCR were performed to identify how the PBEC differentiated under ALI culture condition. Both models were exposed to palladium (Pd) nanoparticles which sized 6-10 nm, analogous to those released from modern car catalysts, at three different concentrations utilizing the XposeALI module of the PreciseInhale® exposure system.

Results: Exposing the 3D models to Pd nanoparticles induced increased secretion of IL-8, yet the chronic bronchitis-like model released significantly more IL-8 than the normal model. The levels of IL-8 in basal medium (BM) and apical lavage medium (AM) were in the same ranges, but the secretion of MMP-9 was significantly higher in the AM compared to the BM.

Conclusion: This combination of relevant human bronchial mucosa models and sophisticated exposure system can mimic in vivo conditions and serve as a useful alternative animal testing tool when studying adverse effects in humans exposed to aerosols, air pollutants or particles in an occupational setting.

MeSH terms

  • Air Pollutants / toxicity*
  • Bronchi / drug effects*
  • Bronchi / metabolism
  • Environmental Exposure*
  • Humans
  • Inflammation Mediators / metabolism
  • Metal Nanoparticles / toxicity*
  • Models, Biological*
  • Mucous Membrane / drug effects
  • Mucous Membrane / metabolism
  • Palladium / toxicity*

Substances

  • Air Pollutants
  • Inflammation Mediators
  • Palladium

Grants and funding

Support was provided to: LP by the Swedish Fund for Research without Animal Experiments (grant no. 22/10, 40/11, F35/12, F25/13, F34-14 and F36/15); LP, VK, PG by: Swedish Research Council (grant no. 521-2010-2801 and 2014-02767); LP by the Swedish Heart-lung Foundation (grant no. 20100180, 20120376, 20120818, 20150328, 20150329 and 20150330); and LP by the Karolinska Insitutet. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.