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Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of the alpha 6 beta 4 and alpha 6 beta 1 integrins on epidermal Langerhans cells (LC) before and after mast cell degranulation was studied in cultured human neonatal foreskin by immunohistochemistry. Twenty-four hours after addition of mast cell secretagogues, morphine sulfate, or substance P, solitary mid-epidermal cells showed staining for the integrin subunits alpha 6, beta 4, and beta 1. This expression was not observed in cultured control explants, and immunostained cells were confirmed to be non-epithelial, dendritic cells by immuno-electron microscopy. The identity of these cells as LC was further established by coincident staining for alpha 6 and CD1a using double immunofluorescence labeling. Addition of tumor necrosis factor-alpha (TNF alpha), the predominant cytokine in mast cell granules, also induced LC to express alpha 6 integrins. Furthermore, preincubation of skin organ cultures with anti-TNF alpha antibodies or the mast cell inhibitor cromolyn sodium abrogated the ability to induce alpha 6 integrins on LC consequent to experimental mast cell degranulation by substance P. These data implicate a role for mast cell-derived TNF alpha in the regulation of the integrins alpha 6 beta 4 and alpha 6 beta 1 on LC. These findings may have important implications relevant to mechanisms for spatial localization of LC within the cutaneous compartments during immune responses.
J Invest Dermatol 1993 Aug
PMID:Mast cell degranulation upregulates alpha 6 integrins on epidermal Langerhans cells. 834 16

In a pilot study designed to investigate immunopathologic events in the evolution of cutaneous lesions in pemphigus foliaceus, we found that in this condition the epidermis is replete with CD68+ dendritic cells. The present study was designed to investigate the nature of this novel intraepidermal CD68+ cell population. For that purpose lesional skin of five patients with PF and, for comparison, of patients with another acantholytic autoimmune disease, pemphigus vulgaris, were examined using a panel of monoclonal antibodies in a three-step immunoperoxidase technique, in an immunofluorescence double-labeling technique, and by immunoelectron microscopy. We found epidermal CD1a+ Langerhans cells significantly decreased in pemphigus foliaceus compared to pemphigus vulgaris, but pemphigus foliaceus and not pemphigus vulgaris epidermis harbored large amounts of bone marrow-derived (CD45+) cells that expressed CD68, HLA-DR, and beta 2-integrin antigens, the most pronounced expression being observed for CD11c and CD18. These epidermal CD68+ cells were of dendritic shape, were CD1a-, and lacked Birbeck granules (BG); however, a small portion of CD68+ cells was also CD1a+ and exhibited BG as revealed by immunoelectron microscopy. These findings demonstrate that in certain conditions, i.e., in pemphigus foliaceus but not in pemphigus vulgaris, there is a shift from CD1a+/CD68- epidermal Langerhans cells towards CD1a-/CD68+ dendritic epidermal cells. The detection of a small number of CD1a+/CD68+/BG+ dendritic epidermal cells may identify these cells as a link between the CD1a+/CD68+/BG+ Langerhans cells and the CD1a-/CD68+/BG- cell population and suggests that these cells represent a transitional form of myelomonocytic cells during their phenotypic and morphologic transformation into resident epidermal Langerhans cells.
J Invest Dermatol 1993 Sep
PMID:CD68 positive epidermal dendritic cells. 837 Sep 61

Extracellular adenosine 5'-triphosphate (ATPo) can induce pore formation in cell membranes, leading to cell permeabilization and eventual cell death. In this study, we examined the sensitivity of human epidermal Langerhans cells to ATP-induced permeabilization and tested the possibility that the Mg(++)- or Ca(++)-dependent plasma membrane ectonucleotidase (mATPase) on Langerhans cells provides protection against the cytotoxic effects of ATPo. Membrane permeability was assessed by using the fluorescent tracer propidium iodide, which confers red nuclear fluorescence to permeabilized cells. Langerhans cells were identified within human epidermal cell suspensions with fluorescein isothiocyanate-conjugated MoAb against CD1a or human leukocyte antigen-DR (HLA-DR) antigens. Cultured human keratinocytes and J774 macrophages were both highly sensitive to permeabilization induced by incubation with ATP (0.5 to 20 mM at 37 degrees C), whereas Langerhans cells were relatively resistant. The non-hydrolyzable ATP analog, adenosine 5'-(beta,gamma-imido) triphosphate, but not other nucleotides such as ADP, AMP, GTP, or UTP, was also able to induce permeabilization comparable to that of ATP, thereby suggesting that ATP hydrolysis is not required for this effect. ATP4- is the moiety most likely responsible for permeabilization, because propidium iodide uptake occurred only when the pH of the medium was > or = 7.4. Permeabilization induced by ATP was augmented by chelation of divalent cations with ethylene-diamine-tetraacetic acid and by the addition of lanthanum or cerium (0.01 to 1 mM). Finally, incubation with the adenosine analog, 5'-p-fluorosulfonylbenzoyl-adenosine (1 mM), inhibited mATPase staining of Langerhans cells in human epidermal sheets, but markedly augmented ATP-induced permeabilization of Langerhans cells. The results indicate that epidermal LC are resistant to the lytic effects of ATPo and that mATPase is involved in such resistance.
J Invest Dermatol 1993 Mar
PMID:Epidermal Langerhans cells are resistant to the permeabilizing effects of extracellular ATP: in vitro evidence supporting a protective role of membrane ATPase. 844 Sep 5

In order to monitor the kinetics of Langerhans cells in the afferent lymph during contact dermatitis, a superficial peripheral lymph vessel draining the skin of the upper and medial part of the foot was cannulated by means of microsurgery on the lower leg of four healthy volunteers. After 2 days an irritant contact dermatitis was induced by application of 10% sodium lauryl sulphate to the area of skin drained by the cannulated lymph vessel. Three days later the spontaneously regressing skin reaction was treated with clobetasol propionate in two of the subjects. Lymph was collected twice daily for 8 days. Langerhans cells were identified by immunofluorescence microscopy of cytocentrifuge slide preparations from the lymph, using a monoclonal anti-CD1a antibody. In the late phase of the contact dermatitis the output, i.e. both the absolute number and the percentage of Langerhans cells in the lymph dramatically increased. At the end of the experiment, when there were no remaining clinical signs of contact dermatitis, the Langerhans cell output still markedly exceeded the initial values. These results are the first direct evidence in humans that migration of Langerhans cells from the skin to the regional lymph nodes is a major feature of irritant contact dermatitis.
Br J Dermatol 1993 Feb
PMID:Large increase of Langerhans cells in human skin lymph derived from irritant contact dermatitis. 845 53

Intercellular adhesion molecule (ICAM)-3 is a recently described member of the immunoglobulin superfamily and, as such, is closely related to ICAM-1 and ICAM-2. All three ICAMS are cognate for the counter-receptor lymphocyte function associated antigen-1 (LFA-1, CD11a/CD18). Unlike ICAM-1 and ICAM-2, ICAM-3 is constitutively expressed at high levels on resting leucocytes. We investigated the expression and function of ICAM-3 in normal skin (n = 5), as well as its expression in psoriasis (n = 4), atopic eczema (n = 4), allergic (rhus) contact dermatitis (n = 3), and cutaneous T-cell lymphoma (CTCL, n = 2). Five-micrometre cryostat sections of skin were stained using monoclonal antibodies to ICAM-3 and a well characterized immunoperoxidase technique. In normal skin, ICAM-3 was expressed by all cutaneous leucocytes but most striking was the strong expression of ICAM-3 by Langerhans cells within both epidermis and dermis. This observation was confirmed by double-labelling with CD1a and negative staining with an IgG1 isotype control. In psoriasis, atopic eczema, allergic contact dermatitis, and CTCL, ICAM-3 was co-expressed on all CD1a+ cells, although, in psoriasis, the intensity of ICAM-3 expression was reduced. Functional blocking experiments were performed to determine whether the observed ICAM-3 expression on Langerhans cells was functionally important in antigen presentation. CD4+ T cells were prepared from peripheral blood and 10(5) CD4+ T cells combined with 10(5) epidermal cells harvested from keratome biopsies of normal skin of an individual allogeneic to the T-cell donor. Addition of 50 micrograms anti-ICAM-3 to the co-culture resulted in a consistent (50%) reduction in degree of alloantigen presentation by Langerhans cells to T cells. Inhibition was 77% of that produced by the addition of anti-LFA-1. These data indicate that ICAM-3 is constitutively expressed by Langerhans cells and is a major ligand for LFA-1 on CD4+ T cells during their response to Langerhans cells. Because fresh Langerhans cells constitutively express little ICAM-1, whereas ICAM-3 is constitutively expressed at high levels, it would appear that ICAM-3 is the dominant functional ICAM on in situ Langerhans cells in the normal epidermis.
Br J Dermatol 1995 Dec
PMID:The ICAM-3/LFA-1 interaction is critical for epidermal Langerhans cell alloantigen presentation to CD4+ T cells. 854 30

The different cell types which migrated 'spontaneously' out of human skin explants during different periods of culture were characterized. Before culture, CD1a+ dendritic cells were observed not only in the epidermis but also in the dermis, whereas CD1b+ dendritic cells were present exclusively in the dermis. The populations of migrating cells were harvested and phenotyped on 3 successive days of culture. They always contained high percentages of CD1a+ cells. The other cells that migrated were T cells and macrophages. A relatively high proportion of the CD1a+ cells that migrated during the first 24 h culture period was also CD1b+. The number of cells which were positive for both CD1a and CD1b decreased in the following 2 days of culture. However, the purified CD1a+ cell populations isolated on the 3 consecutive days did not show any difference in their capacity to stimulate allogeneic T cells. The CD1a+ cells possess potent allo-activating capacities that are independent of whether or not they are positive for CD1b+. Three days after culture about half of the CD1a+ cells were still present in the epidermis and dermis, but no CD1b+ cells could be detected in the dermis. This suggests that the CD1b+ cells represent a population of active migrating cells.
Br J Dermatol 1995 Nov
PMID:Migratory properties and functional capacities of human skin dendritic cells. 855 23

CD86 (B70/B7-2) has recently been identified as an alternative CD28/CTLA-4 ligand on activated B cells. CD86 has also been demonstrated as possibly serving as a primary costimulatory molecule in the initial immune response. Since the human Langerhans cell is one of the most potent antigen-presenting cells, we examined whether CD86 expression and function are found on organ-cultured skin, freshly isolated Langerhans cells, and cultured Langerhans cells in normal human epidermis. Immunohistochemical study in situ revealed that CD86 was expressed on dendritic cells with CD1a antigen in organ-cultured but not fresh skin. Fluorescence-activated cell sorter analysis revealed that no staining for either CD80 or CD86 was observed in freshly isolated Langerhans cells but that both CD80 and CD86 were expressed on cultured Langerhans cells. The actual expression of CD86 on cultured Langerhans cells was further confirmed by the detection of 70-kDa glycoprotein on Western blot analysis. Analysis of polymerase chain reaction demonstrated that both CD80 and CD86 were specifically amplified from purified cultured and freshly isolated Langerhans cells but not from Langerhans cell-depleted epidermal cells, indicating that both CD80 and CD86 genes were expressed by Langerhans cells. The functional importance of CD86 on Langerhans cells was confirmed by the allogeneic CD4 T cell proliferative responses with enriched Langerhans cells. A monoclonal antibody against CD86 caused 81% inhibition in contrast with 29% inhibition produced by anti-CD80 monoclonal antibody. This inhibitory effect was enhanced to 85.3% inhibition when a combination of anti-CD86 and anti-CD80 was administered. These results indicate that CD86 is predominantly expressed on the surface of cultured Langerhans cells and may transduce a primordial costimulatory signal in the interaction of Langerhans cells and T cells.
J Invest Dermatol 1996 Jan
PMID:Functional CD86 (B7-2/B70) on cultured human Langerhans cells. 859 66

Human skin is believed to harbor a reservoir population of precursor melanocytes. It has been difficult to identify these putative cells experimentally, because they lack phenotypic features that define mature melanocytes. We have evaluated expression of the KIT tyrosine kinase receptor, which is critical for melanocyte development, as a possible marker of these cells. Sections of human skin were evaluated with single- and double-immunolabeling techniques. KIT-reactive dendritic cells were identified in the basal layer of the epithelia and were most numerous in the follicular infundibula and the rete ridges. These cells were located on the epithelial side of the basement membrane and lacked expression of cytokeratin and mast cell tryptase. The location of the KIT-reactive cells was distinctly different from that of Langerhans cells (identified with anti-CD1a) or Merkel cells (identified with CAM 5.2). Within the epidermis and upper follicular infundibulum the majority of the KIT-reactive dendritic cells also coexpressed TRP-1, a marker present in differentiated melanocytes. In the deeper follicular regions, the coexpression of TRP-1 in the KIT-reactive cells was absent. Throughout the epidermis and follicle, however, the KIT-reactive cells coexpressed BCL-2, a marker known to be increased in melanocytes. Thus, KIT expression reveals a population of intraepithelial cells that have immunophenotypic characteristics of mature melanocytes within the upper epithelial regions, but lack the differentiated melanocytic phenotype within the deeper follicular regions. We propose that these KIT(+), BCL-2(+), and TRP-1(-) cells constitute a precursor melanocyte reservoir of human skin.
J Invest Dermatol 1996 May
PMID:KIT expression reveals a population of precursor melanocytes in human skin. 861 59

We investigated epidermal cell suspensions prepared from lesional and nonlesional atopic eczema skin, other inflammatory skin conditions, and normal human skin for high-affinity IgE receptor (Fc epsilon RI) expression on dendritic CD1a cells by quantitative flow cytometric analysis. A single CD1a bright/CD1b neg/Fc epsilon RI dim/CD23 neg/CD32 dim/HLA-DR bright/CD36 neg population was found in normal skin. In contrast, lesional skin of atopic eczema and other inflammatory skin diseases harbored variable proportions of two distinct CD1a populations. Both populations exhibited typical ultrastructural features of Langerhans cells, but the second one lacked Birbeck granules and was unreactive to the Birbeck granule-specific LAG antibody. Both populations differed phenotypically: classical Langerhans cells were CD1a bright/CD1b neg/Fc epsilon RI dim/CD23 neg/CD32 dim/HLA-DR bright/CD36 dim, while the second population was CD1a dim/CD1b dim/Fc epsilon RI bright/CD23 dim/CD32 dim/HLA-DR bright/CD36 bright. The highest Fc epsilon RI expression was found on the second CD1a population in lesional atopic eczema skin. Furthermore, Fc epsilon RI expression on CD1a cells correlated significantly with the serum IgE level of the patients. Thus, a distinct population of CD1a inflammatory dendritic epidermal cells different from classical Langerhans cells appears in the epidermis of lesional skin and is subjected to specific signals leading to the upregulation of Fc epsilon RI in atopic eczema skin.
J Invest Dermatol 1996 Mar
PMID:Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema. 864 75

Determination was made of epidermal Langerhans cell (LC) distribution and infiltrating cellular events in lesional skin during varicella zoster virus (VZV) infection, and the results were compared with those for herpes simplex (HS), measles, and rubella by immunohistochemical staining with cell surface markers. CD1a positive epidermal LCs increased in number, particularly in measles and rubella. The number of LCs was within the normal range or slightly increased in the epidermis of VZV infection. In herpes zoster (HZ) and varicella, HLA-DR positive epidermal cells were present in the basal part of the epidermis. In measles, HLA-DR positive cells aggregated in papular lesions. In measles and rubella, the number of HLA-DQ positive epidermal cells appeared to increase. In HS cases, CD11b (OKM1) positivity of the upper epidermal keratinocytes was quite pronounced, but not in the basal layer. CD8 positive suppressor/cytotoxic cells extensively infiltrated the dermis of HZ and varicella. Dermal infiltrates were identified as CD8 positive cell dominant in measles, HZ, and varicella. These results provide a partial explanation as to why cellular events in skin lesions act immunosuppressively.
J Dermatol 1996 Jan
PMID:Immunohistochemical study of cellular events in lesional skin during common virus infections. 872 Feb 54


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