1. Introduction
Cobalt is a transition metal widely used in rechargeable batteries, hard metal industry, jewelry and painting. Five cobalt compounds and cobalt metal itself have been classified as category 1 sensitizers [1]. Cobalt chloride has been identified as a potent skin sensitizer [2], based on the mouse local lymph node assay (LLNA). Epidemiological studies have demonstrated a higher risk of asthma in workers exposed to cobalt [3, 4], and several case series of cobalt-induced asthma have also been reported [5, 6].
Although several studies identified cobalt as an asthmagen, the mechanisms are still unclear. In a systematic review of animal studies involving almost 30 chemical sensitizers, we have concluded that respiratory responses – especially airway hyper-reactivity (AHR) – to the administration of a sensitizer via the airways are more pronounced in animals having been previously exposed to the chemical via the skin, compared with controls without prior dermal exposure [7]. The evidence for this phenomenon is limited for metals with sensitizing potential.
One of the unresolved questions is whether skin exposure/sensitization to cobalt can lead to asthma-like symptoms when the airways are subsequently exposed to cobalt. In a well-validated mouse model, we have shown this mechanism for several chemicals [8–10]. In animal asthma models, neutrophils and eosinophils in BAL have long been considered as indicators of airway inflammation. Moreover, emerging evidence has revealed the role of innate lymphoid cells (ILCs) [11] and dendritic cells (DCs) [12] in the pathogenesis of asthma.
The hypothesis of this experimental study was that our asthma model consisting of skin sensitization followed by airway challenge, which we had validated for several organic chemicals [7], would also be applicable to a relevant metallic sensitizer, such as cobalt. We also investigated whether a low-dose µCT approach was able to identify early changes in the lungs after the airway challenges in a non-invasive manner. Finally, we assessed for the first time the involvement of innate lymphoid cells (ILC) and dendritic cells (DC) in the immune responses induced in the lungs by prior dermal exposure to a sensitizer.