Abstract
Photoactivation and binding of photoactive chemicals to proteins is a known prerequisite for the formation of immunogenic photoantigens and the induction of photoallergy. The intensive use of products and the availability of new chemicals, along with an increasing exposure to sun light contribute to the risk of photosensitizing adverse reactions. Dendritic cells (DC) play a pivotal role in the induction of allergic contact dermatitis. Human peripheral blood monocyte derived dendritic cells (PBMDC) were thus perceived as an obvious choice for the development of a novel in vitro photosensitization assay using the modulation of cell surface protein expression in response to photosensitizing agents. In this new protocol, known chemicals with photosensitizing, allergenic or non-allergenic potential were pre-incubated with PBMDCs prior to UVA irradiation (1 J/cm2). Following a 48 h incubation, the expression of the cell surface molecules CD86, HLA-DR and CD83 was measured by flow cytometry. All tested photosensitizers induced a significant and dose-dependent increase of CD86 expression after irradiation compared to non-irradiated controls. Moreover, the phototoxicity of the chemicals could also be determined. In contrast, (i) CD86 expression was not affected by the chosen irradiation conditions, (ii) increased CD86 expression induced by allergens was independent of irradiation and (iii) no PBMDC activation was observed with the non-allergenic control. The assay proposed here for the evaluation of the photoallergenic potential of chemicals includes the assessment of their allergenic, phototoxic and toxic potential in a single and robust test system and is filling a gap in the in vitro photoallergenicity test battery.
Highlights
Phototoxicity, photoirritancy and photoallergy are topically induced health hazards that can be induced by sun light (UV/vis radiation) in the presence of photoreactive agents, generally referred to as ‘‘photosensitizers’’
UV-light sensitivity of peripheral blood monocyte derived dendritic cells (PBMDC) In particular ultraviolet radiation (UVA and UVB) can induce various biological effects including a modulation of the human immune response through phenotypical and functional changes in antigen presenting cells or even functional damage of macrophages, Langerhans or dendritic cells, which can result in an impaired antigen presentation capacity and a suppression of the immune response
To evaluate the magnitude of that variability, we investigated the basal CD86, CD83 and HLA-DR surface expression in non-irradiated and irradiated PBMDCs obtained from more than 40 different donors
Summary
Phototoxicity, photoirritancy and photoallergy are topically induced health hazards that can be induced by (simulated) sun light (UV/vis radiation) in the presence of photoreactive agents, generally referred to as ‘‘photosensitizers’’. Due to the public concern regarding the use of animals and the increasing test volume owing to the number of newly developed chemicals the need for innovative in vitro alternatives was recognized well before the acceptance of the amendment. Years ago industrial research groups have developed and validated the 3T3 Neutral Red Uptake (NRU) phototoxicity test [1]. These activities resulted in the acceptance by the EU and the OECD acute phototoxicity test guideline No 432. This guideline test can be performed on fibroblasts or keratinocytes in order to identify the phototoxic potential of a chemical [2]. To date no accepted alternative is available to identify the photoallergenic potential of a new chemical
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