Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal Langerhans cells (LC) may occur in subsets with different phenotypic and functional characteristics. In this work give further evidence that the CD1a-positive LC population in the normal human epidermis may be heterogeneous. We found that one of our monoclonal antibodies (TE4B) to stratum corneum chymotryptic enzyme (SCCE) stained a population of dendritic cells in the normal epidermis in addition to high suprabasal keratinocytes. The staining of the dendritic cells was seen only when the biopsies had been fixed with formaldehyde and when the sections had been pretreated, either with proteolytic enzymes or with Triton X-100. The binding of the antibody was mediated through its antigen binding site, as it could be inhibited by adsorption with recombinant pro-SCCE. Experiments with double labelling showed that the TE4B-positive dendritic cells were also CD1a-positive. On the other hand, not all CD1a-positive cells were TE4B-positive. By means of confocal microscopy of double-labelled cells, the TE4B binding site could be localized intracellularly. SCCE-mRNA could be detected by in situ hybridization in high suprabasal keratinocytes only. A possible explanation may be that there is a subset of LC which have taken up SCCE secreted by high suprabasal keratinocytes. Alternatively, TE4B may bind to an epitope present in a subgroup of epidermal LC which cross-reacts immunologically with SCCE. It is suggested that the demonstrated heterogeneity of the population of LC in the normal epidermis should be taken into account in studies on the possible role of epidermal autoantigens in the development of immune-mediated skin diseases.
Br J Dermatol 1997 May
PMID:In situ evidence that the population of Langerhans cells in normal human epidermis may be heterogeneous. 920

The human CD1a molecule is a transmembrane protein which shares structural similarities with HLA class I molecules. It has restricted tissue distribution in normal individuals, and is a useful diagnostic marker for certain disease states such as Langerhans cell histiocytosis. In order to investigate the function of this molecule, a cDNA fragment encoding the CD1a molecule was cloned into several EUKARYOTIC expression vectors which were then used to establish human epithelial cell lines stably expressing the membrane-bound CD1a molecule. Human keratinocytes (HaCaT) and epithelial cells (HeLa) stably expressing CD1a were established by retroviral-mediated gene transfer and DNA transfection, respectively. Expression and localization of the CD1A molecule were then confirmed by Northern blot analysis and immunofluorescence methods. CD1a expression appears to have profound effects on cellular growth and morphology. Both stably CD1a-expressing HeLa and HaCaT cells showed increased doubling times, and up to 20% of CD1a-expressing cells showed altered cell morphology. Clonogenicity experiments demonstrated a reduction in colony size and plating efficiency was augmented in CD1a-positive cells when compared with vector-transfected/infected controls. Our findings suggest that CD1A expression may act as a negative growth regulator in these cells in vitro. Furthermore, lower temperatures greatly enhanced the expression of CD1a at both the protein and mRNA levels in a time-dependent fashion. Since the physiological skin temperatures lie well below the core temperature, this observation may have important implications in the study of Langerhans cells in vitro.
Arch Dermatol Res 1997 May
PMID:Stable expression of CD1a molecule in human epithelial cell lines shows temperature-dependent expression and affects cell morphology and growth. 920 82

Recently, we reported the functional expression of CD86 on cultured human Langerhans cells derived from normal epidermis. In the present study, we investigated the expression and function of co-stimulatory molecules in the pathogenesis of atopic dermatitis. In immunohistochemical analysis, CD80 and/or CD86 were detected on dendritic-shaped cells not only in the epidermis but also in the dermis in the inflammatory lesions of atopic dermatitis (n = 12). CD80 was expressed in only five cases (42%), while CD86 was expressed in all cases (100%). These molecules were not detected in normal control subjects (n = 8). In non-lesional skin of atopic dermatitis (n = 4), CD86 but not CD80 was detected in one case. CD86 was preferentially induced on dendritic-shaped cells in positive patch test sites to Dermatophagoides pteronyssinus or house dust allergen in atopic dermatitis (n = 4). The CD80- or CD86-positive cells were confirmed as Langerhans cells by double immunostaining using anti-CD1a monoclonal antibody. Neither CD86 nor CD80 was detected on keratinocytes. Similar results of the stronger expression of CD86 over that of CD80 were obtained from psoriasis vulgaris (n = 11) and from contact dermatitis (n = 7), although CD86 was expressed only in 57% of the contact dermatitis cases. The percentage of Langerhans cells positive for CD86 was higher than for CD80, i.e. 48% compared with 9%, respectively, in the epidermis of lesional skin of atopic dermatitis (n = 8). The expression rate of these molecules on Langerhans cells increased in the dermis. To investigate the function of co-stimulatory molecules on Langerhans cells in atopic dermatitis, we conducted an inhibition test with antibodies. Anti-CD86 monoclonal antibody almost completely inhibited T-cell proliferation stimulated with crude extract of D. pteronyssinus in the presence of epidermal cells as antigen-presenting cells, whereas anti-CD80 monoclonal antibody produced less of an inhibitory effect. These data indicate that CD86 expressed on Langerhans cells may play an important part in the pathogenesis of atopic dermatitis.
Br J Dermatol 1997 Jun
PMID:Functional CD86 (B7-2/B70) is predominantly expressed on Langerhans cells in atopic dermatitis. 960 93

The densities of feline epidermal dendritic cells expressing CD18, MHC class II and CD1a antigens were determined for four anatomical locations in 19 cats of European breed in blind conditions. The densities (+/- SD) of CD1a+ Langerhans cells in the skin of the abdominal wall (269 +/- 68 cells/mm2), the back (363 +/- 19), the internal side of the ear (572 +/- 30) and the external side of the ear (502 +/- 32) were significantly different, with young and old animals displaying less stained cells than adults. No significant differences in the mean densities were found with regard to sex, colour or antibody used.
Br J Dermatol 1997 Jun
PMID:Quantitative assessment of feline epidermal Langerhans cells. 921 37

An unusual case of Langerhans cell histiocytosis in a 7-year-old female is presented. She had ultrastructural evidence of desmosomal biogenesis and formation of gland-like structures by lesional cells; their apical plasma membranes were folded into large numbers of microvilli. Despite the presence of these structures characteristic of epithelial cells, an infiltrated plaque on the abdominal skin of this patient was interpreted as cutaneous involvement of multiple system Langerhans cell histiocytosis because the immunohistochemical staining of the lesional cells for CD1a, S100, PNA, CD4, EN-4, and HLA-DR was positive, and numerous Birbeck granules were ultrastructurally identified in some lesional cells. Other clinical data included the presence of scaly erythematous skin lesions on the forehead and lytic osseous lesions in the maxilla, which were also histologically diagnosed as Langerhans cell histiocytosis. The absence of any internal malignancy in this patient readily ruled out the other diagnostic possibility of a metastatic adenocarcinoma showing glandular differentiation with brush border morphogenesis. The possibility that the desmosome-linked lesional epithelioid cells were actually cells of sweat glands entrapped in the histiocytic proliferation was also ruled out. The functional significance of the desmosomes and microvillous structures in the present case of Langerhans cell histiocytosis remains to be clarified. Awareness of this variant of Langerhans cell histiocytosis will be important for averting potential misdiagnosis in favor of epithelial tumors, especially metastatic adenocarcinomas.
J Dermatol 1997 Jun
PMID:Langerhans cell histiocytosis (histiocytosis X) with morphologic expression of desmosomes and microvillous structures. 924 66

The majority of in vitro reconstructed human epidermis is composed of keratinocytes only. Recently, the introduction of melanocytes into epidermal reconstructs has enlarged their field of application. The completion of reconstructed epidermis by introducing Langerhans cells remained an important challenge because Langerhans cells, unlike the other epidermal cell types, cannot be subcultured and expanded. To solve this problem, we used cord blood-derived CD34+ hematopoietic progenitors. Seeding these cells, after induction of their differentiation by granulocyte macrophage-colony stimulating factor and tumor necrosis factor-alpha, onto a reconstructing epidermis, composed of keratinocytes and melanocytes, gives rise to a pigmented epidermis with melanocytes in the basal layer and resident epidermal Langerhans cells located suprabasally. Interestingly, the same result was obtained by co-seeding a mixture of keratinocytes, melanocytes, and nondifferentiated CD34+ hematopoietic progenitors on the dermal equivalent, indicating that keratinocytes provide the environmental conditions for hematopoietic progenitors to differentiate into resident epidermal Langerhans cells, expressing major histocompatibility complex class II molecules, CD1a antigen, and Birbeck granules.
J Invest Dermatol 1997 Oct
PMID:Integration of Langerhans cells into a pigmented reconstructed human epidermis. 932 82

In this study, we investigated the effect of ultraviolet B radiation on human Langerhans cell function. Normal human skin was irradiated ex vivo with single doses of ultraviolet B. For assessment of T-cell stimulatory function, cells that spontaneously migrated from epidermal sheets were used, whereas full-thickness skin biopsies were used to investigate alterations in migratory properties. The cells migrating from ultraviolet B-exposed epidermal sheets demonstrated a decrease in the percentage of HLA-DR positive Langerhans cells, as well as a reduced capacity to induce proliferation of allogeneic T cells, when compared with cells migrating from nonexposed sheets. When a correction was made for the decreased number of HLA-DR positive Langerhans cells migrating from ultraviolet B-exposed epidermis, however, it appeared that the capacity to induce T-cell proliferation was identical for Langerhans cells migrating from ultraviolet B-exposed and nonexposed epidermis. The presence of ultraviolet B-induced DNA damage could be demonstrated in the Langerhans cells from ultraviolet B-treated skin, indicating that the cells had received significant doses of ultraviolet B. As regards the effect of ultraviolet B on migratory properties of Langerhans cells, we found not only that reduced numbers of CD1a-positive Langerhans cells migrated from the ultraviolet B-exposed full-thickness skin, but also that there was a reduction in CD1a-positive Langerhans cells in the epidermis. This implies that ultraviolet B induces death of Langerhans cells as well as loss of cell surface molecules rather than altering Langerhans cells migration, whereas the Langerhans cells that were still able to migrate fully retained the capacity to activate allogeneic T cells.
J Invest Dermatol 1997 Nov
PMID:Despite the presence of UVB-induced DNA damage, HLA-DR+ cells from ex vivo UVB-exposed human skin are able to migrate and show no impaired allostimulatory capacity. 934 89

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.
Br J Dermatol 1997 Sep
PMID:Presence of somatostatin in normal human epidermis. 934 32

Calcipotriene is a synthetic analogue of 1,25-dihydroxyvitamin D3 established to be effective topically in the treatment of psoriasis. We investigated the early cellular and immunological events induced by calcipotriene in psoriasis. Thirty patients with moderate plaque-type psoriasis were randomly assigned to receive twice daily applications of either calcipotriene ointment 0.005% or matching vehicle for 6 weeks. Skin biopsies (6 mm) were performed from designated plaques at baseline and days 3 and 7. On these days and at weeks 2, 4 and 6, complete clinical evaluations were made in a double-blind fashion. Consistent with previous studies, significant clinical improvement (P < 0.05) in psoriasis was observed in patients receiving calcipotriene vs. those receiving vehicle by day 7 for scale and erythema, and by day 14 for thickness. No significant improvement, however, was seen on day 3. None of the immunohistological markers (CD1a, CD4, CD8, ICAM-1, VCAM-1, E-selectin, HLA-DR) semiquantitatively assessed in psoriatic plaques was significantly changed by calcipotriene treatment for 7 days. In the calcipotriene-treated group, interleukin (IL)-10 levels (pg/microgram of protein) increased by 57% from baseline (0.030 +/- 0.006; mean +/- SEM) to day 3 (0.047 +/- 0.011) (P = 0.05 vs. baseline; n = 10) and remained elevated at day 7 (0.046 +/- 0.012). IL-8 levels (pg/microgram of protein), however, declined by 70% from baseline (0.13 +/- 0.06) to day 3 (0.04 +/- 0.01), and remained low at day 7 (0.03 +/- 0.02) (P < 0.05 vs. baseline; n = 10). Both IL-8 and IL-10 were unaffected by vehicle treatment. Calcipotriene-induced clinical improvement of psoriasis is preceded by an increase in IL-10 and a concomitant decrease in IL-8 levels. The changes in the level of these two cytokines provide further evidence for immunological changes as a significant part of the mechanism of action of calcipotriene in psoriasis.
Br J Dermatol 1998 Jan
PMID:Calcipotriene-induced improvement in psoriasis is associated with reduced interleukin-8 and increased interleukin-10 levels within lesions. 953 26

Recently, a novel type of dendritic antigen-presenting cell has been identified in the dermis of normal human and mouse skin. These dermal dendritic cells (DDC) occur in higher numbers than epidermal Langerhans cells, represent a distinct differentiation pathway of dendritic cells, and are as potent as Langerhans cells in the activation of superantigen specific T cells. As yet, nothing is known about their capacity to take up, process, and present soluble protein antigens. We used the model of tetanus toxoid (TT) driven T cell proliferation to address these questions. To test for active internalization of TT protein, gold labeled TT was incubated with Langerhans cells and DDC and could be traced to multivesicular endo-lysosomal compartments. DDC internalize TT through a receptor-mediated, clathrin-independent pathway, whereas Langerhans cells predominantly use macropinocytosis. To verify that DDC process TT by the exogenous pathway of antigen presentation, we pulsed DDC with TT protein or TT peptide after preincubation with chloroquine. Preincubation with chloroquine diminished the capacity of DDC to induce TT protein specific T cell proliferation (70-80%), but was not effective to suppress TT peptide induced T cell responses. DDC were as potent as Langerhans cells and 5-10 x more potent than plastic adherent monocytes in the presentation of TT to autologous resting T cells. Furthermore, as few as 50 DDC (stimulator:responder ratio of 1:1000) were able to induce a significant TT specific T cell proliferation. Because a subpopulation of DDC expresses low levels of CD1a, a phenotypic marker of Langerhans cells, sorting of CD1a positive and negative DDC was performed. On a per cell basis, CD1a positive and negative DDC were equally potent at mediating TT specific T cell proliferation. Thus, DDC are able to internalize, process, and present soluble protein antigens such as TT and may therefore play an important role in the regulation of skin immune responses.
J Invest Dermatol 1998 May
PMID:Human dermal dendritic cells process and present soluble protein antigens. 957 42


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