Expression of functional kappa-opioid receptors on murine dendritic cells.

Endogenous and exogenous opioids are known to exert direct effects on the immune system and the expression of functional opioid receptors has been reported for several immune cell types. Since dendritic cells are important inducers and regulators of immune responses, we investigated whether murine dendritic cells express functional kappa-opioid receptors. FACScan analysis and radioligand binding studies revealed the expression of kappa-opioid receptors by murine dendritic cells, which by RT-PCR were also shown to express kappa-opioid mRNA. In a primary allogenic mixed-lymphocyte reaction the kappa-agonists dynorphin A and U50488H suppressed the capacity of dendritic cells to induce T-cell proliferation in a concentration-dependent manner. Preincubation with the kappa-specific antagonist nor-binaltrophimine abolished the observed effect, indicating specificity. In contrast, antigen uptake by dendritic cells as well as phenotypic maturation of dendritic cells were not influenced by the kappa-agonists dynorphin A and U50488H. In summary our data demonstrate that dendritic cells express functional kappa-opioid receptors and that specific agonists exert a direct effect on these cells. Therefore, dendritic cells might be involved in the interaction of the neuroendocrine hormones and the immune system.

CC and CXC chemokines are differentially expressed in erythema multiforme in vivo.

BACKGROUND: A characteristic feature of erythema multiforme is an acute inflammatory reaction of the skin with an infiltrate largely composed of mononuclear cells around the upper dermal vessels and in the dermal-epidermal interface. OBJECTIVE: To determine the composition and localization of leukocyte subsets and corresponding expression of chemokines with chemoattractant properties for lymphocytes and macrophages. MATERIALS AND METHODS: Immunohistochemical analysis was performed to localize leukocyte subsets (CD1(+), CD3(+), CD4(+), CD8(+), and CD68(+)). Expression of transcripts and proteins of chemokines (macrophage chemoattractant protein [MCP] 1); macrophage inflammatory protein [MIP] 1 alpha and MIP-1 beta; regulated on activation, normal T-cell expressed and secreted [RANTES]; growth-related oncogene alpha; epithelial-derived neutrophil attractant 78; interleukin 8; macrophage interferon-gamma inducible gene [Mig]; and interferon-gamma inducible protein 10) was determined by in situ hybridization and immunohistochemical analysis. SETTING: Department of Dermatology, University of Würzburg Medical School. RESULTS: High levels of messenger RNA expression of MCP-1, RANTES, Mig, and interferon-gamma inducible protein 10 were detected and localized in the interface zone and subepidermal infiltrate. In contrast, other investigated chemokines (growth-related oncogene alpha, interleukin 8, epithelial-derived neutrophil attractant 78, I-309, MIP-1 alpha, and MIP-1 beta) were minimally expressed or absent. Protein expression of MCP-1, RANTES, Mig, and interferon-gamma inducible protein 10 was high in the interface zone and low in the subepidermal infiltrate. The messenger RNA expression and protein immunoreactivity patterns overlapped. According to the expression profiles, Mig, interferon-gamma inducible protein 10, MCP-1, and RANTES were expressed by basal keratinocytes above and mononuclear cells within the inflammatory foci. CONCLUSION: These cytokines are important agents in the cytokine network and contribute to the cell-specific and spatially restricted recruitment of mononuclear cells in the acute inflammation of erythema multiforme lesions.