Nickel remains the primary cause of contact allergy, despite efforts to minimize exposure. Nickel is classified as a hapten, a small molecule that, upon combining with proteins, evokes an immune response. To determine the mechanism involved in contact allergy, a team of scientists from Chalmers University and University of Gothenburg, Sweden, has investigated the penetration and distribution of this hapten through the human skin using imaging mass spectrometry. Their results indicate a new method for investigation of skin distribution of contact allergens, providing an alternative to animal experiments (Contact Dermatitis 78 109).

Exposure to nickel

Imaging mass spectrometry is a valuable analytical tool that uses a beam of primary ions to visualize the spatial distribution of chemical molecules on a surface by their molecular mass. The researchers chose time-of-flight secondary ion mass spectrometry (ToF-SIMS) for this study as it provides high-resolution images.

They exposed samples of human skin (obtained from breast reduction surgery) for 24 h to a nickel sulphate solution; control samples were exposed to deionized water. Both the samples from the tissue exposed to nickel and the control tissue were frozen in liquid nitrogen, sliced and analysed by ToF-SIMS.

Nickel distribution

Analysis of the ToF-SIMS images generated a visualization of the distribution of nickel ions as a function of depth into the sample. The results indicated that the highest intensity of nickel ions was observed in the stratum corneum (the outermost layer of the epidermis, regarded as the major barrier to chemical transfer through the skin). The authors observed a lower density of nickel ions in the upper epidermis, as well as a rapid decrease in the number of nickel ions with skin depth.

Moreover, the authors reported that collagen (one of the most abundant proteins in our body and the building block to the health of our skin) is not found in the stratum corneum but at the interface between the epidermis and the dermis (the inner layer of the skin). Collagen was found there together with lipids with a low mass (such as cholesterol and phosphatidylcholine (PC) headgroup). Surprisingly, these remained unaffected by the nickel sulphate exposure. In contrast, lipids with higher mass were found to have an altered biomolecular composition compared with control tissue, indicating a physiological effect due to nickel sulphate exposure.

This study is the first to offer information regarding penetration of a hapten in human skin ex vivo and validates ToF-SIMS as a tool to acquire high-resolution images of ion distribution in different layers of the skin. This approach may be expanded for investigation of other skin sensitizers, thus providing new avenues for chemical testing while representing a way to reduce the number of animal experiments.