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.