Dermal exposure determines the outcome of repeated airway exposure in a long-term chemical-induced asthma-like mouse model

Pollaris, Lore; Broucke, Sofie Van Den; Decaesteker, Tatjana; Cremer, Jonathan; Seys, Sven; Devos, Fien; Provoost, Sharen; Maes, Tania; Verbeken, Erik; Velde, Greetje Vande; Nemery, Benoît; Hoet, Peter; Vanoirbeek, Jeroen

doi:10.1016/j.tox.2019.05.001

Cited by 12 publications

(9 citation statements)

References 44 publications

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“…This suggests a role for sensitization at the skin or gastrointestinal tract. Indeed, Pollaris et al demonstrated for toluene diisocyanate that dermal sensitization, before repeated intranasal challenges, could induce an aggravated lymphocyte proliferation in lymph nodes and even airway hyperreactivity [39]. Thus, in our study, sensitization to CS with the whole-body system might have provoked an aggravated in ammatory response in the lungs during CS exposure.…”

Section: Discussionmentioning

confidence: 45%

Enhanced Lung Inflammatory Response in Whole-body Compared to Nose-only Cigarette Smoke-exposed Mice

Serré

Tanjeko

Mathyssen

et al. 2020

Preprint

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Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by a progressive and abnormal inflammatory response in the lungs, mainly caused by cigarette smoking. Animal models exposed to cigarette smoke (CS) are used to mimic human COPD but the use of different CS protocols makes it difficult to compare the immunological and structural consequences of using a nose-only or whole-body CS exposure system. We hypothesized that when using a standardized CS exposure protocol based on particle density and CO (carbon monoxide) levels, the whole-body CS exposure system would generate a more severe inflammatory response than the nose-only system, due to possible sensitization, uptake of gases through the skin or uptake of tar particles stuck on the skin via grooming. Methods: In this study focusing on early COPD, mice were exposed twice daily 5 days a week to CS either with a nose-only or whole-body exposure system for 14 weeks to assess lung remodeling and inflammation. Data was analyzed with a one-way ANOVA with Bonferroni post-hoc test or Kruskal-Wallis with Dunn’s test for multiple comparison depending on respectively parametric or non-parametric datasets.Results: Both CS exposure systems induced a similar degree of lung function impairment and morphological alterations. Interestingly, an enhanced lymphoid presence in the bronchoalveolar lavage and lymph nodes with a higher mRNA expression of interleukin 6 and keratinocyte chemoattractant in the lungs were found with the whole-body system. Conclusion: Our data indicate that the inflammatory outcomes are more severe in the whole-body CS exposure compared to the nose-only system, but lung remodeling and lung function impairment are similarly affected. These observations can assist researchers to make an appropriate choice between the two CS exposure systems in designing their future studies in early drug interventions.

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Section: Discussionmentioning

confidence: 45%

Enhanced Lung Inflammatory Response in Whole-body Compared to Nose-only Cigarette Smoke-exposed Mice

Serré

Tanjeko

Mathyssen

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…This suggests a role for sensitization at the skin or gastrointestinal tract. Indeed, Pollaris et al demonstrated for toluene diisocyanate that dermal sensitization, before repeated intranasal challenges, could induce an aggravated lymphocyte proliferation in lymph nodes and even airway hyperreactivity [42]. Thus, in our study, sensitization to CS with the whole-body system might have provoked an aggravated inflammatory response in the lungs during CS exposure.…”

Section: Discussionmentioning

confidence: 46%

Enhanced lung inflammatory response in whole-body compared to nose-only cigarette smoke-exposed mice

et al. 2021

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Background Chronic obstructive pulmonary disease (COPD) is characterized by a progressive and abnormal inflammatory response in the lungs, mainly caused by cigarette smoking. Animal models exposed to cigarette smoke (CS) are used to mimic human COPD but the use of different CS protocols makes it difficult to compare the immunological and structural consequences of using a nose-only or whole-body CS exposure system. We hypothesized that when using a standardized CS exposure protocol based on particle density and CO (carbon monoxide) levels, the whole-body CS exposure system would generate a more severe inflammatory response than the nose-only system, due to possible sensitization by uptake of CS-components through the skin or via grooming. Methods In this study focusing on early COPD, mice were exposed twice daily 5 days a week to CS either with a nose-only or whole-body exposure system for 14 weeks to assess lung function, remodeling and inflammation. Results At sacrifice, serum cotinine levels were significantly higher in the whole-body (5.3 (2.3–6.9) ng/ml) compared to the nose-only ((2.0 (1.8–2.5) ng/ml) exposure system and controls (1.0 (0.9–1.0) ng/ml). Both CS exposure systems induced a similar degree of lung function impairment, while inflammation was more severe in whole body exposure system. Slightly more bronchial epithelial damage, mucus and airspace enlargement were observed with the nose-only exposure system. More lymphocytes were present in the bronchoalveolar lavage (BAL) and lymph nodes of the whole-body exposure system while enhanced IgA and IgG production was found in BAL and to a lesser extent in serum with the nose-only exposure system. Conclusion The current standardized CS-exposure protocol resulted in a higher internal load of serum cotinine in the whole-body exposure system, which was associated with more inflammation. However, both exposure systems resulted in a similar lung function impairment. Data also highlighted differences between the two models in terms of lung inflammation and remodelling, and potential sensitization to CS. Researchers should be aware of these differences when designing their future studies for an early intervention in COPD.

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“…cDC2s and moDCs are known to facilitate Th2 and Th17 cell differentiation (23,24), which is also in accordance with the cytokine pattern from our study. Though some studies have evaluated the shifting of pulmonary DC subtypes after respiratory exposure to sensitizing agents (24,26), the shifting after solely skin exposure has never been reported.…”

Section: Discussionmentioning

confidence: 99%

Cobalt exposure via skin alters lung immune cells and enhances pulmonary responses to cobalt in mice

Tsui

Decaesteker

Jonckheere

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

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Background: Cobalt has been associated with allergic contact dermatitis and occupational asthma. However, the link between skin exposure and lung responses to cobalt is currently unknown. We investigated the effect of prior dermal sensitization to cobalt on pulmonary physiological and immunological responses after subsequent challenge with cobalt via the airways. Methods: BALB/c mice received epicutaneous applications (25 μl/ear) with 5% CoCl2*6H2O (Co) or the vehicle (Veh) dimethyl sulfoxide (DMSO) twice; they then received oropharyngeal challenges with 0.05% CoCl2*6H2O or saline five times, thereby obtaining four groups: Veh/Veh, Co/Veh, Veh/Co and Co/Co. To detect early respiratory responses non-invasively, we performed sequential in vivo micro-computed tomography (µCT). One day after the last challenge, we assessed airway hyper-reactivity (AHR) to methacholine, inflammation in bronchoalveolar lavage (BAL), innate lymphoid cells (ILCs) and dendritic cells (DCs) in lung, and serum IgE. Result: Compared with the Veh/Veh-group, the Co/Co-group showed increased µCT-derived lung response, increased AHR to methacholine, mixed neutrophilic and eosinophilic inflammation, elevated monocyte chemoattractant protein-1 (MCP-1) and elevated keratinocyte chemoattractant (KC) in BAL. Flow cytometry in the Co/Co-group demonstrated increased DC, type 1 and type 2 conventional DC (cDC1/cDC2), monocyte-derived DC, increased ILC group 2 and NCR-ILC group 3. The Veh/Co-group showed only increased AHR to methacholine and elevated MCP-1 in BAL, whereas the Co/Veh-group showed increased cDC1 and ILC2 in lung. Conclusion: We conclude that dermal sensitization to cobalt may increase the susceptibility of the lungs to inhaling cobalt. Mechanistically, this enhanced susceptibility involves changes in pulmonary DCs and ILCs.

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Dermal exposure determines the outcome of repeated airway exposure in a long-term chemical-induced asthma-like mouse model

Cited by 12 publications

References 44 publications

Enhanced Lung Inflammatory Response in Whole-body Compared to Nose-only Cigarette Smoke-exposed Mice

Enhanced Lung Inflammatory Response in Whole-body Compared to Nose-only Cigarette Smoke-exposed Mice

Enhanced lung inflammatory response in whole-body compared to nose-only cigarette smoke-exposed mice

Cobalt exposure via skin alters lung immune cells and enhances pulmonary responses to cobalt in mice

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