Assessment of Carbon Nanotubes on Barrier Function, Ciliary Beating Frequency and Cytokine Release in In Vitro Models of the Respiratory Tract

Claudia Meindl; Markus Absenger-Novak; Ramona Jeitler; Eva Roblegg; Eleonore Fröhlich

doi:10.3390/nano13040682

Assessment of Carbon Nanotubes on Barrier Function, Ciliary Beating Frequency and Cytokine Release in In Vitro Models of the Respiratory Tract

Nanomaterials (Basel). 2023 Feb 9;13(4):682. doi: 10.3390/nano13040682.

Authors

Claudia Meindl¹, Markus Absenger-Novak¹, Ramona Jeitler², Eva Roblegg², Eleonore Fröhlich¹

Affiliations

¹ Center for Medical Research, Medical University of Graz, Stiftingtalstr. 24, 8010 Graz, Austria.
² Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, Universitaetsplatz 1, 8010 Graz, Austria.

Abstract

The exposure to inhaled carbon nanotubes (CNT) may have adverse effects on workers upon chronic exposure. In order to assess the toxicity of inhaled nanoparticles in a physiologically relevant manner, an air-liquid interface culture of mono and cocultures of respiratory cells and assessment in reconstructed bronchial and alveolar tissues was used. The effect of CNT4003 reference particles applied in simulated lung fluid was studied in bronchial (Calu-3 cells, EpiAirway™ and MucilAir™ tissues) and alveolar (A549 +/-THP-1 and EpiAlveolar™ +/-THP-1) models. Cytotoxicity, transepithelial electrical resistance, interleukin 6 and 8 secretion, mucociliary clearance and ciliary beating frequency were used as readout parameters. With the exception of increased secretion of interleukin 6 in the EpiAlveolar™ tissues, no adverse effects of CNT4003 particles, applied at doses corresponding to the maximum estimated lifetime exposure of workers, in the bronchial and alveolar models were noted, suggesting no marked differences between the models. Since the doses for whole-life exposure were applied over a shorter time, it is not clear if the interleukin 6 increase in the EpiAlveolar™ tissues has physiological relevance.

Keywords: alveolar epithelium; bronchial epithelium; carbon nanotubes; ciliary beating frequency; in vitro models; respiratory tract; toxicity.

Grants and funding

PETA Science Consortium International e.V. supported this research with an Award from MatTek Life Sciences for 3D human tissue models to assess respiratory toxicity to E.F.