Skin Langerhans cells

With respect to vasodilation, niacin-elicited vasodilation requires the activation of GPR109A in skin Langerhans cells [34,35], which then triggers the release of arachidonic acid from membrane phospholipids and its subsequent metabolism to PGD2. The production of PGD2 then activates DPI receptors in dermal blood vessels to cause vasodilation [36]. 

Decreased epidermal proliferation is considered to be the main mechanism of action of PUVA in the treatment of psoriasis. Once excited by UVA, psoralens can react with molecular oxygen, producing reactive oxygen species that cause mitochondrial dysfunction and lead to apoptosis of skin Langerhans cells, keratinocytes, and lymphocytes [134]. PUVA further decreases epidermal cell proliferation by noncompetitively binding to epidermal growth factor receptors and directly altering the cell surface membrane. 

Wollenberg A. Kraft S. Hanau D. Bieber T Immuno-morphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell population in lesional skin of atopic eczema. J Invest Dermatol 1996 106 446-453. 

Bieber T. Braun-Falco O IgE-bearing Langerhans cells are not specific to atopic eczema but are found in inflammatory skin diseases. J Am Acad Dermatol 1991 24 658-659. 

Toews, G. B., Bergstresser, R R., and Streilein, J. W., Epidermal Langerhans cell density determines whether contact hypersensitivity or unresponsiveness follows skin painting with DNFB, J. Immunol. 124, 445 449, 1980. 

Ingested arsenic localizes to the skin [2, 7], where it may alter cutaneous immune responses. The delayed type hypersensitivity (DTH) response to 2,4-dinitrochlorobenzene (DNCB) was suppressed in Bowen s disease patients [8], Langerhans cells (LC) in skin lesions and perilesioned skin from arsenic-induced Bowen s disease and carcinomas were reduced in number and were morphologically altered, having a notable loss of dendrites [9], These data suggest that chronic exposure to arsenic in drinking water may... 

Type IV Delayed-type Hypersensitivity (DTH). Delayed-type hypersensitivity reactions are T-cell mediated with no involvement of antibodies. However, these reactions are controlled through accessory cells, suppressor T cells, and monokine-secreting macrophages, which regulate the proliferation and differentiation of T cells. The most frequent form of DTH manifests itself as contact dermatitis. The drug or metabolite binds to a protein in the skin or the Langerhans cell membrane... 

The mechanisms of autoimmunity may also entail interaction with MHC structures determined by the HLA alleles. Individuals carrying certain HLA alleles have been shown to be predisposed to certain autoimmune diseases, which may account in part for the genetic variability of autoimmunity. In addition, metabolites of a particular drug may vary between individuals to confound the development of drug-induced autoimmunity. Dendritic cells, such as the Langerhans cells of the skin and B lymphocytes that function to present antigens to Th cells, express class-II... 

Type IV hypersensitivity responses are elicited by T lymphocytes and are controlled by accessory cells and suppressor T cells. Macrophages are also involved in that they secrete several monokines, which results in proliferation and differentiation of T cells. Thus, there are numerous points along this intricate pathway in which drugs may modulate the final response. To achieve a Type IV response, an initial high-dose exposure or repeated lower-dose exposures are applied to the skin the antigen is carried from the skin by Langerhans cells and presented to cells in the thymus to initiate T-cell proliferation and sensitization. Once sensitized, a second challenge dose will elicit an inflammatory response. Thus, before sensitivity can be assessed, each of the models used to evaluate dermal hypersensitivity requires as a minimum ... 

Therefore, liposomes, and also nanoparticles, may allow for the development of needle-less vaccination systems. Studies on mice inoculated with influenza DNA vaccine complexes with liposomes and SLN already demonstrated a clear T-cell (predominantly Thl-type) response. Therefore, the immune response appears to be mediated by Langerhans cells, which is the immune competent cell in the skin (for review, see [65]). 

In the context of skin sensitization bioavailability can be seen as the capacity of the compound to reach the viable epidermis, where it interacts with keratinocytes and Langerhans cells. This capacity is dependent on its molecular weight and solubility in polar and apolar solvents [115]. Importantly, potency prediction solely on the basis of cell culture models (steps 3 and 4) does not account for skin penetration rate and may thus wrongly predict potency in vivo. Possible in vitro approaches to detect allergic capacity of chemicals/pharmaceuticals are presented in Table 18.5. 

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