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

Abstract

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.

Application-specific approaches to MicroCT for evaluation of mouse models of pulmonary disease

“…These techniques can be applied to multiple models of lung disease development and progression, such as tumor studies, lung transplantation, lung development models, exposure-induced models and in longitudinal studies involving therapeutic intervention. Several novel techniques for image acquisition and analysis have been recently published [1,2,[17][18][19], however, a standardized method has yet to be established, and there are currently limited published resources for investigators to determine appropriate imaging and analysis approaches to meet study requirements. Herein, we describe four approaches to microCT with detailed methodological information and discussion of advantages and limitations of each approach.…”