Biological impact of sequential exposures to allergens and ultrafine particle-rich combustion aerosol on human bronchial epithelial BEAS-2B cells at the air liquid interface

March 16, 2023

doi: 10.1002/jat.4458

Elias Josef Zimmermann 1 2, Joana Candeias 3, Nadine Gawlitta 1, Christoph Bisig 1, Stephanie Binder 1 2, Jana Pantzke 1 2, Svenja Offer 1 2, Narges Rastak 1 2, Stefanie Bauer 1, Anja Huber 2, Evelyn Kuhn 2, Jeroen Buters 3, Thomas Groeger 1, Mathilde N Delaval 1, Sebastian Oeder 1, Sebastiano Di Bucchianico 1 2, Ralf Zimmermann 1 2

1Joint Mass Spectrometry Centre (JMSC), Cooperation Group Comprehensive Molecular Analytics, Helmholtz Zentrum München, Neuherberg, Germany.
2Joint Mass Spectrometry Centre (JMSC), Chair of Analytical Chemistry, University of Rostock, Rostock, Germany.
3Center for Allergy and Environment (ZAUM), Technical University Munich, Munich, 80802, Germany.

This study examined the effects of combustion-derived ultrafine particles aerosol on bronchial epithelial cells with or without pre-treatment to common indoor and outdoor allergens, i.e. house dust mite and birch pollen extracts, using air-liquid interface exposure techniques to mimic human lung exposure.

The prevalence of allergic diseases is constantly increasing since few decades. Anthropogenic ultrafine particles (UFPs) and allergenic aerosols is highly involved in this increase; however, the underlying cellular mechanisms are not yet understood. Studies observing these effects focused mainly on singular in vivo or in vitro exposures of single particle sources, while there is only limited evidence on their subsequent or combined effects. Our study aimed at evaluating the effect of subsequent exposures to allergy-related anthropogenic and biogenic aerosols on cellular mechanism exposed at air-liquid interface (ALI) conditions. Bronchial epithelial BEAS-2B cells were exposed to UFP-rich combustion aerosols for 2 h with or without allergen pre-exposure to birch pollen extract (BPE) or house dust mite extract (HDME). The physicochemical properties of the generated particles were characterized by state-of-the-art analytical instrumentation. We evaluated the cellular response in terms of cytotoxicity, oxidative stress, genotoxicity, and in-depth gene expression profiling. We observed that single exposures with UFP, BPE, and HDME cause genotoxicity. Exposure to UFP induced pro-inflammatory canonical pathways, shifting to a more xenobiotic-related response with longer preincubation time. With additional allergen exposure, the modulation of pro-inflammatory and xenobiotic signaling was more pronounced and appeared faster. Moreover, aryl hydrocarbon receptor (AhR) signaling activation showed to be an important feature of UFP toxicity, which was especially pronounced upon pre-exposure. In summary, we were able to demonstrate the importance of subsequent exposure studies to understand realistic exposure situations and to identify possible adjuvant allergic effects and the underlying molecular mechanisms.

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