Expression of substance P receptors in normal and psoriatic skin.

Recently, substance P receptors (SPR) have been detected in neonatal foreskin. Our purpose was to determine the expression of SPR in other localizations than neonatal foreskin. As SP has been implicated in the pathogenesis of inflammatory cutaneous lesions, we wondered whether SPR localization was modified in psoriatic lesions. In normal skin, SP binding sites were detected using biotinylated SP and abrogated by a specific NK1 antagonist (spantide) on blood vessels, sweat glands and hair follicles. In the normal epidermis, SPR were usually observed on granular layers but may also be observed on other cell layers. The SP binding processed on cultured keratinocytes demonstrated that SPR were expressed in the epidermis, except basal cell layers, confirming that keratinocytes constitutively express SPR. In skin lesions of psoriatic patients, SP binding sites were expressed on the uppermost keratinocytes which are not granular cells, and seem to be overexpressed. Our results raise the question of the role of SPR on psoriatic keratinocytes.

Modulation of cutaneous SP receptors in atopic dermatitis after UVA irradiation.

Atopic dermatitis is a pruritic inflammatory skin disorder, involving immunological and non-immunological factors. Substance P seems to be involved in the pathogenesis of atopic dermatitis. Substance P-containing nerve fibers are increased in the lesional skin of patients with atopic dermatitis and a reduced weal and flare reaction to intradermal injection of substance P has been observed. We investigated the distribution of substance P receptors in the involved skin of patients before and after single or repetitive UVA irradiations. Our results indicate that substance P receptors of the NK-1 subtype are expressed on blood vessels and on epidermal keratinocytes of involved skin of patients with atopic dermatitis. UVA irradiations did not modify the epidermal distribution of substance P receptors but decreased their expression intensity on blood vessels. UVA irradiations seem to decrease skin inflammation through the modulation of NK-1 receptor expression on endothelial cells.

Effect of UVB 311 nm irradiation on normal human skin.

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1+ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a+ cells and a moderate increase of HLA-DR+ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1+ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.

Binding and in vitro modulation of human epidermal Langerhans cell functions by substance P.

Substance P (SP) is distributed in both the central and peripheral nervous system. It has various effects on immunocompetent cells, such as macrophages and lymphocytes. The aim of our study was to search for the presence of SP receptors (SP-R) on human cutaneous Langerhans cells (LC), and to determine the effects of SP on LC immunological functions in a model of mixed epidermal cell-lymphocyte reaction (MELR). Radioligand binding studies showed that LC-enriched epidermal cell suspensions reversibly bound SP, and that the specific binding increased with the percentage of LC. Functional assays showed that SP had no effect when added at concentrations from 10(-6) M to 10(-12) M to the MELR. The addition of SP at concentrations of 10(-4) M and 10(-5) M was able to inhibit the allogeneic T-cell response (98.3 +/- 1.8% and 92.8 +/- 8.9% inhibition, respectively) without modifying the cell viability. This inhibition was through an effect of SP on both T-cell and LC function. We conclude that SP has receptors on LC and may inhibit antigen presentation.

[Substance P and human skin]. / Substance P et peau humaine.

Substance P (SP) is a neuropeptide that is a neurotransmitter and a neuromodulator in the central and peripheral nervous system. SP is known to have regulatory effects on nervous or non nervous cells, including immune cells. SP is involved in the physiopathology of local inflammation, including inflammatory dermatoses. The purpose of this review is to relate the localization of SP and its receptors to illustrate the immunomodulatory functions of SP through its effects on various immune cells and to focus on the localization of SP in human skin and on its effects on cutaneous cells. The probable implication of SP in inflammatory dermatoses will be discussed.

Expression of gastrin-releasing peptide receptor in human skin.

Bombesin-related peptides are expressed in the skin of batrachians and mammals. As gastrin-releasing peptide belongs to this family, we searched for the presence and distribution of gastrin-releasing peptide receptors (GRPr) in the skin of healthy human adults by immunohistochemistry, flow cytometry and electron microscopy. The results indicated that GRPr are expressed on nerves and vessels in the dermis, on eccrine sweat glands, sebaceous glands and erector pili muscle. Within epidermis, staining was localized only on basal and suprabasal layer cells, or in the whole epidermis, according to the samples studied. Interestingly, suprabasal epidermal dendritic cells occasionally showed a strong labelling. Some of these epidermal dendritic cells were identified as Langerhans' cells by immunoelectron microscopy studies. Flow cytometry analysis of crude epidermal cell suspensions resulted in the expression of GRPr on about 43% of the cells. Therefore, we investigated whether human GRPr could modulate Langerhans' cells antigen-presenting functions. For this purpose, we added increasing concentrations of GRP (10(-12) to 10(-5) M) to mixed epidermal cell lymphocyte reactions. Allogeneic T-cell proliferation was not significantly modified when added to GRP-pretreated epidermal cells. In conclusion, we demonstrated the presence of GRPr in human skin, suggesting that GRP may modulate epidermal cell functions but does not modify antigenic presentation.