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)

In human epidermis, expression of CD1a is confined to Langerhans cells (LC), whereas CD1c expression has been observed in dendritic cells of the dermis, as well as the epidermis. In transfected fibroblasts, expression of CD1c at the cell surface appears to exclude expression of either CD1b or CD1a, despite continued transcription of the latter genes. In order to determine whether this mechanism might be operative in human skin, we have compared the expression of CD1a and CD1c on the surface of dermal and epidermal dendritic cells to their expression at the level of mRNA using a combination of dual-label immunofluorescence microscopy, northern blot hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR). By both immunofluorescence and Northern blotting, CD1c expression was observed in both dermal and epidermal cells, whereas expression of CD1a was confined largely to the epidermis. Moreover, as shown by immunomagnetic bead selection and RT-PCR, CD1a and CD1c were both expressed on epidermal LC, but were absent from other epidermal cell types. These results argue against cell surface exclusion as a mechanism for selective expression of CD1c in human dermis.
J Dermatol Sci 1993 Dec
PMID:CD1 gene expression in human skin. 751 Sep 98

We have analysed Langerhans cells (LCs) in basal cell carcinoma (BCC) and in healthy skin in 15 patients, using three different techniques: light microscopic examination of horizontal sheets, and of 6-micron-thick vertical skin sections, and confocal laser scanning microscopy (CLSM) of 25-micron-thick vertical sections. The use of CLSM enables both a quantitative and a three-dimensional (3-D) analysis of the cells in the same tissue volume. A statistically significant reduction in the relative volume of epidermal CD1a reactivity confined to tumour areas was found with CLSM. This difference was confirmed when the number of LCs in horizontal sheets were counted. In contrast, no significant reduction in epidermal CD1a+ cells was found in thin vertical sections. This is probably due to the smaller tissue sample examined, and to variations in the number of CD1a+ cells, with less cells directly overlying the tumour nests. The ratio of CD1a-expressing cells in the epidermis/dermis was significantly reduced in BCCs, compared with healthy looking skin. Few LCs were observed in tumour nests, but they were numerous in the surrounding stroma of the dermis. Three-dimensional reconstructions of CD1a+ cells in BCC revealed striking morphological changes; they had a reduced number of dendrites, and these were often short and had few branches. The results demonstrate that CLSM is a suitable technique for quantitative and morphological analysis of CD1a-expressing cells in the skin. We suggest that the alterations in LC numbers, distribution and morphology in BCC most probably are secondary to changes in the local environment.
Br J Dermatol 1994 Mar
PMID:Quantitative and 3-dimensional analysis of Langerhans cells in basal cell carcinoma. A comparative study using light microscopy and confocal laser scanning microscopy. 751 26

A proposed role for antigen-presenting dermal dendrocytes in the pathogenesis of many dermal inflammatory skin diseases remains speculative. We therefore sought to determine the phenotype and functional characteristics of antigen-presenting cells isolated from normal human dermis. Normal adult human skin was incubated overnight with dispase at 4 degrees C, the epidermis was removed, and the residual dermal preparation was then minced and digested with a mixture of hyaluronidase, collagenase, and DNAase at 37 degrees C, prior to filtration through mesh. Dermal cell suspensions thus obtained were stained using specific monoclonal antibodies, and analysed by fluorescence microscopy or flow cytometry. Mean values were as follows: CD45+ leucocytes 39%, HLA-DR+ cells 39%, Ulex europaeus agglutinin I+ endothelial cells 26%, CD1a+ cells 3.9%, CD11b+ cells 16%, CD11c+ cells 6%. Mitomycin C-treated crude dermal cell suspensions induced allostimulation of peripheral blood mononuclear cells in a 7-day culture, as assessed by 3H-TdR incorporation. Depletion of CD1a+ Langerhans-like cells from the dermal cell preparation, by 95, 74 and 90% in three separate experiments using immunomagnetic beads, reduced 3H-TdR incorporation at optimal responder-to-stimulator cell ratios by 90, 64, and 87%, respectively. Our findings suggest that, in normal human dermis, the great majority of the alloantigen-presenting capacity resides in the CD1a+ Langerhans cell-like dendritic antigen-presenting cell population, and not to any great extent in either CD1a- macrophage-like cells, or HLA-DR+ endothelial cells. The relationship of the CD1a+ dermal antigen-presenting cells to the Langerhans cell lineage remains to be determined.
Br J Dermatol 1994 Jul
PMID:Antigen-presenting capacity in normal human dermis is mainly subserved by CD1a+ cells. 754 20

Interactions of CD28 (on T cells) with its recently identified ligand B7/BB1 (on antigen-presenting cells) have been shown to activate T cells via a major histocompatibility complex/Ag-independent "alternative" pathway, leading to an amplification of T-cell-mediated immune responses. The in vivo relevance of these molecules for cutaneous immunity is presently unknown. These findings prompted us to study the expression of B7/BB1 and CD28 in normal human skin and in selected T-cell-mediated inflammatory skin diseases. Biopsies were obtained from lesional skin of patients with allergic contact dermatitis, lichen planus, and, as control, from basal cell carcinoma and from healthy controls. Serial cryostat sections were stained with a panel of MoAbs directed against CD28, B7/BB1, CD3, CD1a, and KiM8 using immunohistochemistry (ABC technique). CD28 expression was observed in the majority of dermal and epidermal CD3+ T cells in contact dermatitis and lichen planus. In normal skin and basal cell carcinoma, CD28 was expressed only occasionally by perivascular T cells. In allergic contact dermatitis and lichen planus, B7/BB1-expression was found on dermal dendritic cells, on dermal macrophages, on Langerhans cells, focally on keratinocytes, and occasionally on dermal T cells. No B7/BB1 immunoreactivity was detected in normal skin and basal cell carcinoma. These findings indicate that T-cell-mediated skin diseases are accompanied by an influx of CD28+ T cells and an upregulation of B7/BB1 on cutaneous antigen-presenting cells, keratinocytes, and on some T cells. We speculate that "alternative" T cell-activation via the B7/CD28 pathway may contribute to the pathogenesis of these skin diseases.
J Invest Dermatol 1994 Oct
PMID:Expression of the B7/BB1 activation antigen and its ligand CD28 in T-cell-mediated skin diseases. 752 32

Epidermal Langerhans cell heterogeneity is poorly understood with regard to phenotypic characteristics, such as the expression of human leukocyte antigen (HLA)-DR, integrin, and Fc receptor molecules, as well as functional characteristics, such as the ability to process and present antigens or produce cytokines during various phases of immigration and maturation. Technical limitations of Langerhans cell number have limited functional assays on putative Langerhans cell subsets in in vivo epidermis. Therefore, we used flow cytometry for simultaneous phenotypic and functional assessment at the single-cell level within the Langerhans cell population. Freshly isolated human epidermal cell suspensions were stained with a battery of monoclonal antibodies, including anti-HLA-DR, -CD1a, -CD1c, -CD11c, -Fc gamma RII, and -Fc epsilon RI. Two distinct Langerhans cell subsets were identified by their different levels of HLA-DR expression. The DRHi subset expressed higher amounts of CD11c and exhibited greater cytoplasmic complexity and higher baseline calcium than the DRLo subset (p < or = 0.03 for each). Some subjects also expressed high levels of Fc epsilon RI in the DRHi, CD11cHi subset. To determine whether these phenotypic subsets may exhibit differential signal-transduction functional properties, Langerhans cells were partially enriched over Ficoll-Hypaque and their cytosolic mobilization after the addition of ionomycin was analyzed using the calcium indicator, indo-1, in conjunction with quantitative analysis of HLA-DR expression. By this real-time flow cytometric analysis, a new subpopulation was revealed within the DRLo Langerhans cell subset. This subset increased its cytosolic calcium concentration much more than the other two subsets (change in indo-1 blue:violet emission ratio of 37.33 +/- 2.34 in the Hi Flux DRLo subset versus 13.23 +/- 0.29 in the Lo Flux DRLo subset, and versus 7.6 +/- 2.99 in the Lo Flux DRHi subset). These data indicate that functional, as well as phenotypic, subsets of Langerhans cells exist within normal human epidermis. Their responses to physiologic stimuli may relate to maturational stage or the level of in vivo activation.
J Invest Dermatol 1995 Jan
PMID:Differential responsiveness of Langerhans cell subsets of varying phenotypic states in normal human epidermis. 752 45

The family of protein kinase C (PKC) isoenzymes plays a fundamental part in signal transduction, and thereby regulates important cellular functions, including growth, differentiation, cytokine production and adhesion molecule expression. In lesional psoriatic skin, Ca(2+)-dependent PKC activity, PKC-beta protein and epidermal Langerhans cell (LC) PKC-beta immunostaining are significantly decreased, indicating activation and subsequent down-regulation of PKC. Whether these changes occur in other inflammatory/hyperplastic dermatoses is, however, unknown. We examined PKC-alpha and PKC-beta expression in normal skin, psoriasis, cutaneous T-cell lymphoma (CTCL), lamellar ichthyosis, non-bullous ichthyosiform erythroderma, atopic dermatitis, urushiol-induced allergic contact dermatitis, and sodium lauryl sulphate (SLS)-induced irritant contact dermatitis. Cryostat sections were stained for PKC-alpha and PKC-beta, and the LC marker CD1a, using an immunoperoxidase technique and specific monoclonal antibodies. Double-labelling studies, in normal skin, revealed co-expression of PKC-beta and CD1a by epidermal LCs. Analysis of the number of PKC-beta+ and CD1a+ epidermal LCs, in diseased compared with normal skin, revealed three categories: (i) in psoriasis and CTCL, the PKC-beta+ epidermal LC number was significantly reduced, whereas the CD1a+ epidermal LC number was unchanged; (ii) in allergic and irritant contact dermatitis, both PKC-beta+ and CD1a+ epidermal LCs were significantly reduced in number; and (iii) in atopic dermatitis, the PKC-beta+ epidermal LC number was normal, and CD1a+ epidermal LCs were significantly increased in number. Moreover, the ratio of epidermal LC PKC+/CD1a+ was reduced in all the dermatoses studied, suggesting activation of PKC-beta, with subsequent down-regulation. Within the dermis, increased PKC-beta staining of infiltrating cells was observed in all the conditions studied except lamellar ichthyosis and non-bullous ichthyosiform erythroderma. These data indicate that: (i) down-regulation of LC PKC-beta occurs in a variety of inflammatory and hyperplastic skin disorders, and is not unique to psoriasis, and (ii) the pattern of epidermal LC PKC-beta and CD1a expression varies among the diseases studied. In mice, PKC activation induces LC migration. Thus, down-regulation of epidermal LC PKC-beta associated with reduced CD1a+ epidermal LCs in allergic and irritant contact dermatitis suggests that PKC-beta may transduce the signal for migration of LCs from human epidermis.
Br J Dermatol 1995 Aug
PMID:Down-regulation of Langerhans cell protein kinase C-beta isoenzyme expression in inflammatory and hyperplastic dermatoses. 754 80

Detailed studies on the biology of Langerhans cells (LC), which account for only 1-3% of all epidermal cells, require isolation from their cutaneous symbionts. Several techniques of LC isolation have been reported, including positive enrichment with mAb coupled to immunomagnetic beads. The disadvantage of this technique is the size of the beads (approximately 2-5 microns), which can interfere with subsequent phenotypic and functional analyses. This limitation prompted us to test whether paramagnetic microbeads (15 nm) employed by the MACS system could be used to purify LC from human skin. To isolate fresh LC (fLC), epidermal cell suspensions (EC) were stained with anti-CD1a mAb and with appropriate secondary reagents conjugated to microbeads and to FITC. They were then passed over a separation column and exposed to a strong magnetic field. Thereafter both CD1a-depleted and CD1a-enriched cells were collected. Cultured LC (cLC) were isolated by staining 72-h cultured EC with anti-HLA-DR mAb followed by the same isolation procedure. Using this technique, we could routinely isolate viable EC that were 45-88% CD1a+ or HLA-DR+ as determined by FACS. Two-color FACS analysis demonstrated the majority of MACS-purified cells to be CD1a+/HLA-DR+, indicating that they were indeed LC. By transmission electron microscopy (TEM), the MACS-purified CD1a+/HLA-DR+ cells showed typical ultrastructural characteristics of LC. Furthermore, MACS-purified fLC or cLC were functionally intact, because they stimulated the proliferation of alloreactive T cells in a primary, one-way, mixed epidermal cell leukocyte reaction (MECLR). We conclude that MACS-separation is an efficient and rapid method to isolate human fLC and cLC of high purity and unimpaired function.
Exp Dermatol 1995 Jun
PMID:Rapid purification of human Langerhans cells using paramagnetic microbeads. 755 63

Recently, it has been demonstrated that the skin-infiltrating T cells express cutaneous lymphocyte-associated antigen, which is the ligand of E-selectin or endothelial-leukocyte adhesion molecule, suggesting that cutaneous lymphocyte-associated antigen functions as the homing receptor of the skin infiltrating T cells. In contrast, the mechanism for the migration of Langerhans cells from the bone marrow to the skin has not been clarified. Sialyl LewisX acts as a ligand for endothelial-leukocyte adhesion molecule and granule membrane protein 140. We examined the expression of sialyl LewisX in epidermal dendritic cells in human skin. Two-color immunofluorescence study on an epidermal sheet revealed that human leukocyte antigen DR+ or CD1a+ epidermal dendritic cells were partially sialyl LewisX+, although all of the sialyl LewisX+ dendritic cells were human leukocyte antigen DR+ and CD1a+. Further analysis of these dendritic cells by flow cytometry demonstrated that most of the human leukocyte antigen DR+ and CD1a+ epidermal cells expressed sialyl LewisX, although the magnitude of its expression was more variable than that of CD1a expression, and that some of human leukocyte antigen DR+ cells were clearly sialyl LewisX-. Immunoperoxidase study of normal skin showed the presence of sialyl LewisX+ dendritic cells not only in the epidermis but also in the upper dermis. These data demonstrating the heterogeneity of the expression of sialyl LewisX by epidermal Langerhans cells suggest their possible relationship to the stage of maturation as well as to the migration of Langerhans cells from the bone marrow to the skin.
J Invest Dermatol 1993 Aug
PMID:Sialyl LewisX expression on human Langerhans cells. 768 3

Pathological skin reactions were induced with both UVA and UVB in 12 patients with lupus erythematosus (LE) and with UVA in 7 with polymorphous light eruption (PMLE) but in none of the controls. Biopsy specimens taken from UV-induced lesions showed that in dermal infiltrates of LE cases CD4-positive cells predominated, whereas in the majority of PMLE cases CD8-positive cells predominated. Keratinocytes expressed intercellular adhesion molecule-1 (ICAM-1) in 7 of the 12 UVA- and in eight of the ten UVB-induced LE lesions, and in three of the UVA-induced lesions of PMLE patients. Three different staining patterns were found. In subacute cutaneous LE (SCLE) cases staining throughout the epidermis resembled that seen in genuine SCLE lesions. In discoid LE (DLE) lesions, the staining was most prominent in and near the basal cell layer. In the one systemic LE case and in the PMLE cases, ICAM-1 expression was seen only in association with epidermal spongiosis and T-cell infiltration. Keratinocytes did not express ICAM-1 in the controls or in the non-irradiated skin of the LE patients. In five on the UVA-induced lesions, in eight of the UVB-induced LE lesions and in one of the PMLE cases, keratinocytes expressed CD36. In four of the six LE lesions with fewer CD1a-positive cells, dendritic CD36-positive cells were seen in the epidermis. In conclusion, the pattern of activated keratinocytes and immunocompetent cells in the dermis was similar to that seen in genuine LE and PMLE lesions, but dissimilar to each other and to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Dermatol Res 1993
PMID:Expression of intercellular adhesion molecule-1 (ICAM-1) and OKM5 in UVA- and UVB-induced lesions in patients with lupus erythematosus and polymorphous light eruption. 769 27

Macrophages play important roles in immunity and inflammation, and in allergic, granulomatous and neoplastic diseases. Here, we present the indepth results of an ongoing study of macrophage differentiation pathways in cutaneous macrophage disorders and in vitro. Up to now, a total of 40 cases of cutaneous macrophage disorders (histiocytoses and granulomas) and related diseases were examined using a panel of monoclonal and polyclonal antibodies to macrophage differentiation antigens (mAb MS-1, mAb alpha CD1a, mAb alpha CD34, mAb RM 3/1, mAb alpha CD11c, mAb alpha CD36, mAb MAC 387, mAb 27E10, polyclonal antibodies alpha MRP-8 and -14, mAb alpha CD68, mAb 25F9, mAb DRC1-R4/23, and mAb 1F10). Of these, MS-1 high molecular weight protein, synthesized by non-continuous sinusoidal endothelial cells and highly dendritic perivascular macrophages in normal human organs, is the most specific macrophage differentiation marker. MS-1 high molecular weight protein is selectively expressed by cutaneous non-Langerhans cell histocytoses, and proves to be a valuable diagnostic tool for these diseases. MS-1 high molecular weight protein is not found in Langerhans cell histiocytosis cells, epithelioid cells in sarcoidosis, and palisading histiocytes in granuloma annulare. MS-1+ macrophages may be found intermingled in cellular type dermatofibroma and in foreign body granulomas; they differ from MS-1+ non-Langerhans cell histiocytosis cells by their highly dendritic morphology, and thus rather resemble the MS-1+ macrophages in normal skin. RM 3/1 antigen shows a similar, but broader expression pattern including non-Langerhans cell histiocytoses, xanthelasmata palpebrarum, foreign body granulomas, granuloma annulare, and cellular type dermatofibroma. Moreover, xanthelasmata palpebrarum paradigmatically represent a class of macrophage lesions with strong RM 3/1, but little MS-1 antigen expression. In sarcoidosis, RM 3/1+ macrophages are only found at the very periphery of epithelioid cell granulomas. In contrast, 25F9 antigen is strongly and consistently expressed in epithelioid cells of sarcoidosis, and in foreign body granulomas. In cultured human monocytes/macrophages, RM 3/1 antigen is expressed early on, while MS-1 high molecular weight protein and 25F9 antigen are late and very late macrophage differentiation antigens, respectively. Expression of RM 3/1 antigen and MS-1 high molecular weight protein is inducible by glucocorticoid and interleukin-4, and less so by interleukin-13 and interleukin-10, and combinations thereof, while 25F9 antigen seems to be less influenced by these agents. Interferon-gamma (and less so tumor necrosis factor-alpha) inhibit expression of all three antigens in cultured human monocytes/macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)
Exp Dermatol 1994 Dec
PMID:Dissection of macrophage differentiation pathways in cutaneous macrophage disorders and in vitro. 774 70


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