Biodiesel exhaust particle airway toxicity and the role of polycyclic aromatic hydrocarbons

Ogbunuzor, Christopher C.; Fransen, Leonie Francina Hendrina; Talibi, Midhat; Khan, Zuhaib; Dalzell, Abigail; Laycock, Adam; Southern, Daniel; Eveleigh, Aaron; Ladommatos, Nicos; Hellier, Paul; Leonard, Martin O.

doi:10.1016/j.ecoenv.2023.115013

Cited by 6 publications

(1 citation statement)

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“…Again, due to resource limitation we focussed the majority of the analysis of DEP effects using MLC protocol generated population of cells. Bulk RNA-seq analysis of MLC cells exposed to DEP revealed changes in gene expression consistent with previous understanding of how these particles interact with cells to cause toxic effect 45 – 47 . A large increase in CYP1B1 gene expression, a gene dependent on the aryl hydrocarbon receptor for inducible expression was observed.…”

Section: Discussionsupporting

confidence: 87%

Mononuclear phagocyte sub-types in vitro display diverse transcriptional responses to dust mite exposure

Fransen,

Leonard

2024

Sci Rep

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Mononuclear phagocytes (MNP), including macrophages and dendritic cells form an essential component of primary responses to environmental hazards and toxic exposures. This is particularly important in disease conditions such as asthma and allergic airway disease, where many different cell types are present. In this study, we differentiated CD34+ haematopoietic stem cells towards different populations of MNP in an effort to understand how different cell subtypes present in inflammatory disease microenvironments respond to the common allergen house dust mite (HDM). Using single cell mRNA sequencing, we demonstrate that macrophage subtypes MCSPP1+ and MLCMARCO+ display different patterns of gene expression after HDM challenge, noted especially for the chemokines CXCL5, CXCL8, CCL5 and CCL15. MLCCD206Hi alternatively activated macrophages displayed the greatest changes in expression, while neutrophil and monocyte populations did not respond. Further work investigated how pollutant diesel exhaust particles could modify these transcriptional responses and revealed that CXC but not CC type chemokines were further upregulated. Through the use of diesel particles with adsorbed material removed, we suggest that soluble pollutants on these particles are the active constituents responsible for the modifying effects on HDM. This study highlights that environmental exposures may influence tissue responses dependent on which MNP cell type is present, and that these should be considerations when modelling such events in vitro. Understanding the nuanced responsiveness of different immune cell types to allergen and pollutant exposure also contributes to a better understanding of how these exposures influence the development and exacerbation of human disease.

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Section: Discussionsupporting

confidence: 87%