Air–liquid interface exposure of lung epithelial cells to low doses of nanoparticles to assess pulmonary adverse effects

Silvia Diabaté, Lucie Armand, Sivakumar Murugadoss, Marco Dilger, Susanne Fritsch-Decker, Christoph Schlager, David Béal, Marie Edith Arnal, Mathilde Biola-Clier, Selina Ambrose, Sonja Mülhopt, Hanns Rudolf Paur, Iseult Lynch, Eugenia Valsami-Jones, Marie Carriere, Carsten Weiss

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Reliable and predictive in vitro assays for hazard assessments of manufactured nano-materials (MNMs) are still limited. Specifically, exposure systems which more realistically recapit-ulate the physiological conditions in the lung are needed to predict pulmonary toxicity. To this end, air-liquid interface (ALI) systems have been developed in recent years which might be better suited than conventional submerged exposure assays. However, there is still a need for rigorous side-by-side comparisons of the results obtained with the two different exposure methods considering nu-merous parameters, such as different MNMs, cell culture models and read outs. In this study, human A549 lung epithelial cells and differentiated THP-1 macrophages were exposed under submerged conditions to two abundant types of MNMs i.e., ceria and titania nanoparticles (NPs). Mem-brane integrity, metabolic activity as well as pro-inflammatory responses were recorded. For com-parison, A549 monocultures were also exposed at the ALI to the same MNMs. In the case of titania NPs, genotoxicity was also investigated. In general, cells were more sensitive at the ALI compared to under classical submerged conditions. Whereas ceria NPs triggered only moderate effects, titania NPs clearly initiated cytotoxicity, pro-inflammatory gene expression and genotoxicity. Interest-ingly, low doses of NPs deposited at the ALI were sufficient to drive adverse outcomes, as also documented in rodent experiments. Therefore, further development of ALI systems seems promising to refine, reduce or even replace acute pulmonary toxicity studies in animals.

Original languageEnglish
Article number65
Pages (from-to)1-23
Number of pages23
Issue number1
StatePublished - Jan 2021
Externally publishedYes


  • Alternative methods
  • Cerium dioxide
  • Nanotoxicology
  • Titanium dioxide
  • Zirconium-doping


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