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A Gaudillère

Publications and source records attributed to A Gaudillère.

8 recordsLinked to original sources

Phenotypic and functional outcome of human monocytes or monocyte-derived dendritic cells in a dermal equivalent.

The dermis harbors a true dendritic cell population that could elicit primary allogeneic T cell responses in vitro and contact hypersensitivity reactions in vivo. The origin of dermal dendritic cells remains poorly understood, however. In this study, we analyzed the fate of monocytes or monocyte-derived dendritic cells in a dermal equivalent. Freshly isolated monocytes or monocytes cultured for 6 d with either GM-CSF/IL-4 or GM-CSF/IL-4/TGF-beta 1 (TGF-DC) were seeded in a collagen solution with normal human fibroblasts. The lattices were cultured for 7--14 d in the presence, or absence, of the exogenous cytokines, before phenotypic and functional studies were performed. Supply of exogenous cytokines allows the appearance of typical CD1a(+)/CD14(-)/CD68(low) dendritic cells with significant allostimulatory property, regardless of the cell type incorporated into the lattices. In cytokine-free conditions, monocytes and GM-CSF/IL-4-derived dendritic cells give rise to a CD1a(-)/CD14(+)/CD68(high) monocyte/macrophage population with no allostimulatory property. When incorporated into the lattices in the absence of exogenous cytokines the TGF-DC express few CD68 and FXIIIa. Interestingly, these cells do not all convert into the CD14(+)/CD1a(-) population. Indeed, a small HLA-DR(+)/CD1a(+)/CD14(-) subset was consistently found, which represents about one-third of the HLA-DR(+) cells. Moreover, TGF-DC recovered from the lattices after culture without cytokines do display a significant allostimulatory function. Thus, in the absence of exogenous cytokines, only Langerhans-cell-like dendritic cells can retain the typical dendritic cell features when inserted in a dermal environment. Taken together, these results may provide evidence supporting an epidermal origin of dermal dendritic cells.

Antigens, CD1↗

Human normal dermal fibroblasts express somatostatin receptors.

The hormone/neuropeptide somatostatin (SOM) exerts multiple functions in the central nervous system, the immune system, the hypothalamo-pituitary axis, the gastrointestinal tract, and the pancreas. Endogenous SOM occurs in 2 biologically active forms, with 14 or 28 amino acids. Five subtypes of SOM receptors have been cloned. SOM is present in human skin. We have investigated the expression of SOM receptors on human dermal normal fibroblasts. Biotinyl-SOM allowed the visualization of SOM receptors on human dermal fibroblasts. Radioligand binding studies with (3-[125I]iodotyrosyl11)-SOM-14 were performed on these cells and the effect of SOM-14 on the DNA synthesis by fibroblasts was evaluated by measuring [3H]-methyl thymidine incorporation. Saturation curve, and Scatchard plot showed a homogeneous class of receptors with a Bmax of 0.055 +/- 0.023 nM and KD of 2.0 +/- 0.4 nM (values: mean +/- SEM). Fibroblasts expressed 3,317 +/- 1,385 binding sites per cell. Competitive displacement experiments showed that SOM-14 IC50 was 69.3 +/- 4.5 nM (mean +/- SEM), for SOM-28 33.2 +/- 6.0 nM and for octreotide 36.5 +/- 3.3 nM. The KI values calculated from these IC50 were, respectively: 62.4 +/- 4.1 nM; 29.9 +/- 5.4 nM; 32.9 +/- 2.9 nM. We conclude that subtype 2 or 3 SOM receptors is present on human normal dermal fibroblasts. A weak effect of SOM-14 on DNA synthesis was observed with SOM concentrations of 10(-7) and 10(-6) M.

Animals↗

Presence of somatostatin in normal human epidermis.

Somatostatin (SOM) is a ubiquitous peptide which is responsible for the inhibition of numerous biological functions. SOM is described as an antiproliferative molecule and an inhibitor of exocrine or endocrine secretion from a variety of tissues, including pancreas, gastrointestinal tract, central and peripheral nervous system. Mediation of SOM effects can be indirect or direct, respectively, through other molecules or receptors on target cells. We have searched for the presence of SOM in the epidermis using immunofluorescence, confocal laser scanning microscopy, radioimmunoassay, and chromatography. Immunofluorescence and confocal laser scanning microscopy studies were performed using rabbit antiserum anti-SOM and mouse monoclonal antibody directed to CD1a Langerhans cell (LC) marker disclosed with fluorescein or tetramethylrhodamine isothiocyanate conjugates. SOM was extracted from whole skin or epidermal cell suspension or LC-enriched suspensions and analysed by radioimmunoassay. We used an antiserum which was reactive for the 6-11 portion of native SOM. Chromatographic columns were performed on extracts from whole skin. The epidermis was SOM immunoreactive. LC were immunoreactive for SOM and the staining was membranous. SOM was extracted from the whole skin at about 0.13 +/- 0.02 fmol/mg of tissue (mean +/- SEM). The SOM concentration in epidermal cell suspensions was 1.5 +/- 0.9 fmol/10(6) cells. Data obtained with LC-enriched suspensions showed large variations between donors. Extracts from skin showed one peak with an elution profile like that of 14 amino acid SOM. This study demonstrates that 14 amino acid SOM is expressed in normal human epidermis.

Chromatography, Gel↗

[Merkel cell and neuro-cutaneous system].

The Merkel cell is an epidermal neuroendocrine cell that can be identified by electron microscopy based on its neurosecretory granules or by immunolabeling based on its pattern of cytokeratin expression. Its origin is controversial but may be epidermal rather than neural. Although its functions have not been completely elucidated, there is strong evidence that it produces neuromediators, is involved in the perception of mechanical stimuli, exerts trophic and attractant effects on nerves, stimulates keratinocyte proliferation and differentiation, and plays a role in the spatial organization of the epidermis and epidermal appendages.

Carcinoma, Merkel Cell↗

[Merkel cell].

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Carcinoma, Merkel Cell↗

Expression of PGP9.5 on Langerhans' cells and their precursors.

Langerhans' cells are epidermal dendritic cells, derived from blood precursors. Their main function is antigen presentation to T-cells. They are able to express neuronal proteins, such as neuron-specific enolase or substance P-receptor. They are closely associated with nerve fibres. PGP9.5 is the most specific neuronal protein in the epidermis. Epidermal Langerhans' cells can express PGP9.5 if denervated. Using flow cytometry, we found that cultured CD34+ precursors did not express PGP9.5, whereas suspensions of fresh or cultured Langerhans' cells could express this neuronal protein. Precursors of Langerhans' cells are not able to express PGP9.5, suggesting that they are not mature enough or that the capacity to express PGP9.5 may be acquired only in the epidermis. The function of PGP9.5 on Langerhans' cells and mature dendritic cells remains unknown. PGP9.5 might be related to dendritic cell maturation or to the lack of contacts with nerve endings.

Antigens, Differentiation↗