Fragrance and Contact Allergens in vitro Modulate the HLA–DR and E–Cadherin Expression on Human Epidermal Langerhans Cells

Abstract

Background: Epidermal Langerhans cells (LCs) play a critical role in the induction of contact hypersensitivity. The LCs leave the skin, move to the regional lymph nodes and present the allergens embedded in the HLA–DR molecule to naive T–lymphocytes. To allow LC emigration from the epidermis, E–cadherin must be downregulated. In this study, we have examined the early events that occur in the human epidermis after exposure to three strong contact sensitizers and two commonly used fragrances by examining alterations of E–cadherin and HLA–DR expression. Methods: To determine whether E–cadherin and HLA–DR levels were modulated by allergens, flow cytometry was utilized to evaluate E–cadherin and HLA–DR expression on human epidermal LCs exposed to the different chemicals for 4 h at 37°C. Results: In vitro stimulation with the contact sensitizers isoeugenol, cinnamaldehyde, 2,4,6–trinitrobenzenesulfonic acid, Bandrowski’sbase, or p–phenylene diamine resulted in a dose–dependent decrease of HLA–DR expression on the surface of LCs without affecting the number of positive cells. These contact allergens induced a downregulation of E–cadherin expression as well as a significant decrease of the percentage of E–cadherin–positive cells. Incubation with an irritant, sodium lauryl sulfate, did not significantly change HLA–DR and E–cadherin expression. Conclusions: Based on the alteration of E–cadherin and HLA–DR expression of human LCs under short–term exposure conditions, there was a clear difference between contact sensitizers and a well–characterized irritant. For the first time, the ability of fragrance allergens in dipropylene glycol, a widely used vehicle in fragrance and cosmetic industries, was demonstrated to induce human LC phenotypic alterations. In combination with a series of in vitro tests, this rapid and simple method should help to detect the sensitizing potential of a substance to be applied onto the human skin as an alternative to animal testing.

Acrolein induces activation of the epidermal growth factor receptor of human keratinocytes for cell death

“…UV irradiation to skin lipid has been shown to generate acrolein [Niyati-Shirkhodaee and Shibamoto, 1992] and to cause a number of pathologic skin conditions such as in¯amma-tion, cancer development, and aging [Robinson et al, 1989;Dypbukt et al, 1993;Grafstrom et al, 1994;Coverly et al, 1998;Verrier et al, 1999]. Till present we do not have any data that exactly measured the concentration of acrolein in the UV-irradiated local skin tissue.…”

“…Skin is another target of environmental acrolein, and is the site of endogenous production of acrolein from lipid following ultraviolet (UV) irradiation [Niyati-Shirkhodaee and Shibamoto, 1992]. In skin, acrolein may cause non-immunological contact hypersensitivity [Coverly et al, 1998;Verrier et al, 1999] and can display cytotoxicity and genotoxicity [Robinson et al, 1989;Dypbukt et al, 1993;Grafstrom et al, 1994]. Acrolein is known to act as a potent inhibitor of DNA excision repair enzymes, and this is believed to underlie the acrolein-mediated cytopathic effects [Robinson et al, 1989;Dypbukt et al, 1993;Grafstrom et al, 1994].…”

Modification of cell-surface thiols elicits activation of human monocytic cell line THP-1: Possible involvement in effect of haptens 2,4-dinitrochlorobenzene and nickel sulfate

“…According to the review by Ryan et al (2005), changes in Langerhans cells as a result of exposure to chemical allergens include internalization of surface major histocompatibility complex (MHC) class II molecules via endocytosis (Becker et al, 1992;Girolomoni et al, 1990), induction of tyrosine phosphorylation (Kühn et al, 1998), modulation of cell-surface markers (Aiba and Katz, 1990;Verrier et al, 1999) and changes of cytokine expression (Enk and Katz, 1992).…”

Interleukin-1β and surface marker expression changes induced by tetrachloroplatinate in human monocyte-derived dendritic cells

“…SDS did not significantly affect expression of these antigens [38]. Also, Degwert et al [39] showed that short incubation (up to 3 hrs) of MoDCs with subtoxic concentrations of sensitizers (e.g., NiSO 4 ), but not with irritants (SLS, benzalkonium chloride), down-regulated HLA-DR expression.…”