Uncovering the cytotoxic effects of air pollution with multi-modal imaging of in vitro respiratory models

Author:

Al-Rekabi Zeinab1ORCID,Dondi Camilla1,Faruqui Nilofar1,Siddiqui Nazia S.23,Elowsson Linda4,Rissler Jenny56,Kåredal Monica7,Mudway Ian8910,Larsson-Callerfelt Anna-Karin4,Shaw Michael111ORCID

Affiliation:

1. Department of Chemical and Biological Sciences, National Physical Laboratory, Teddington, UK

2. Faculty of Medical Sciences, University College London, London, UK

3. Kingston Hospital NHS Foundation Trust, Kingston upon Thames, UK

4. Lung Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden

5. Bioeconomy and Health, RISE Research Institutes of Sweden, Lund, Sweden

6. Ergonomics and Aerosol Technology, Lund University, Lund, Sweden

7. Occupational and Environmental Medicine, Lund University, Lund, Sweden

8. MRC Centre for Environment and Health, Imperial College London, London, UK

9. National Institute of Health Protection Research Unit in Environmental Exposures and Health, London, UK

10. Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK

11. Department of Computer Science, University College London, London, UK

Abstract

Annually, an estimated seven million deaths are linked to exposure to airborne pollutants. Despite extensive epidemiological evidence supporting clear associations between poor air quality and a range of short- and long-term health effects, there are considerable gaps in our understanding of the specific mechanisms by which pollutant exposure induces adverse biological responses at the cellular and tissue levels. The development of more complex, predictive, in vitro respiratory models, including two- and three-dimensional cell cultures, spheroids, organoids and tissue cultures, along with more realistic aerosol exposure systems, offers new opportunities to investigate the cytotoxic effects of airborne particulates under controlled laboratory conditions. Parallel advances in high-resolution microscopy have resulted in a range of in vitro imaging tools capable of visualizing and analysing biological systems across unprecedented scales of length, time and complexity. This article considers state-of-the-art in vitro respiratory models and aerosol exposure systems and how they can be interrogated using high-resolution microscopy techniques to investigate cell–pollutant interactions, from the uptake and trafficking of particles to structural and functional modification of subcellular organelles and cells. These data can provide a mechanistic basis from which to advance our understanding of the health effects of airborne particulate pollution and develop improved mitigation measures.

Funder

EMPIR programme, Project AeroTox

Horizon 2020 research and innovation programme

Publisher

The Royal Society

Subject

Multidisciplinary

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