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)

Spleen cells from a BALB/c mouse that had been immunized with human thymocytes were fused with the myeloma line P3-NS 1/1 Ag 4.1. One of the resulting hybrid clones (NA 1/34) secreted an antibody that was highly specific for human thymocytes. Eighty-five % of thymocytes expressed the antigen designated HTA1. There were an estimated 15 x 10(4) molecules of HTA 1 per cell, and it is therefore a major surface molecule. The expression of this antigen on thymocytes appears to be reciprocal to HLA, as recognized by another monoclonal antibody W6/32. Immunoprecipitated material from [125I]-labeled thymocyte membranes was analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate which disclosed a single component of 45,000 molecular weight.
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PMID:A human thymocyte antigen defined by a hybrid myeloma monoclonal antibody. 37 18

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.
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PMID:Mast cell degranulation upregulates alpha 6 integrins on epidermal Langerhans cells. 834 16

FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8 (4-pyridyl) pyrazoro [5-1-c] [1,2,4] triazin-2-yl]-2-phenylethanedion sulfate monohydrate), one of the pyridinyl imidazoles, is an immunosuppressive agent which was developed to inhibit proinflammatory cytokine production. We examined the effect of FR167653 on the differentiation and maturation phases of both human bone marrow-derived dendritic cells (BM-DC) and blood monocyte-derived DC (Mo-DC). DC induced from either BM-DC or Mo-DC progenitors in the presence of FR167653 had lower expression of CD1a, CD83 and CD86 (B7.2). FR167653 also significantly suppressed the ability of Mo-DC to produce both TNF-alpha and IL-1beta in response to LPS stimulation. Mixed lymphocyte reaction (MLR) stimulation was significantly lower in FR167653-treated Mo-DC than in control Mo-DC, although the suppressive effect of FR167653 was much less on BM-DC. These results indicate novel immunosuppressive properties of FR167653, which may be therapeutically useful in controlling chronic immune and/or inflammatory diseases through down-regulation of DC differentiation and maturation.
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PMID:Down-regulation by a new anti-inflammatory compound, FR167653, of differentiation and maturation of human monocytes and bone marrow CD34+ cells to dendritic cells. 1078 47

It has been reported previously that in vitro treatment of human blood derived dendritic cells (DC) with contact allergens provokes the elevated expression of mRNA for interleukin (IL) 1beta, under conditions where similar treatment of cells with the non-sensitizing skin irritant sodium lauryl sulfate (SLS) did not alter IL-1beta mRNA levels (Reutter et al., 1997). The purpose of the present investigation was to evaluate further this phenomenon and to explore the potential utility of this approach for the purpose of skin sensitization testing. Human peripheral blood progenitor cells prepared from healthy adult volunteers were cultured in the presence of IL-4 and granulocyte/macrophage colony stimulating factor. After 5 days of culture, the majority of cells had a Langerhans cell-like phenotype, with characteristic dendritic morphology and cell surface expression of CD83, major histocompatibility complex class II and CD1a determinants. These blood-derived DC were cultured in the presence of the contact allergen 2,4-dinitrofluorobenzene (DNFB), SLS or vehicle alone and mRNA expression for IL-1beta, IL-6 and IL-18 was analysed by semiquantitative reverse transcriptase polymerase chain reaction. Constitutive expression of all three cytokines was observed for DC isolated from all donors examined. Exposure to DNFB resulted in upregulation of IL-1beta mRNA (two- to threefold) in cells derived from three out of eight donors whereas IL-6 and IL-18 were largely unaffected by allergen exposure. In contrast, SLS treatment did not induce IL-1beta mRNA expression in any of the donors investigated. Analysis of cytokine mRNA expression using the protocol described by Reutter et al. (1997), did not increase the sensitivity of measurement of induced cytokine expression. Although selected upregulation of IL-1beta by blood derived DC has been confirmed, a wider range of contact allergens and irritants need to be assessed before this approach could be considered for hazard identification.
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PMID:Investigation of induced changes in interleukin 1beta mRNA expression by cultured human dendritic cells as an in vitro approach to skin sensitization testing. 1090 42

Dendritic cells (DCs) play important roles in initiation and regulation of immune responses. DCs derived from human monocytes can be classified according to presence of CD1a molecules. Although CD1a+ DCs can be prepared from monocytes in media containing GM-CSF, IL-4, and FCS, it has been reported that CD1a+ DCs could not be easily obtained from monocytes using media containing human serum or plasma. In this study, we demonstrate for the first time that heparin can reliably induce differentiation of CD1a+ DCs from monocytes with or without autologous serum or plasma. The development of CD1a+ DCs is heparin concentration dependent (0-50 U/ml). Comparing with CD1a- DCs developed without heparin, CD1a+ DCs express higher CD40 and CD80 and lower CD86. Both CD1a+ and CD1a- DCs express similar levels of HLA-DR. CD80, CD86, HLA-DR, and CD40 are proportionally up-regulated when both types of DCs are stimulated with LPS or LPS plus IFN-gamma. The effect of heparin is neutralized by heparin-binding proteins, such as protamine sulfate, platelet factor-4, and beta-thromboglobulin. Functionally, heparin-treated DCs respond to LPS or LPS plus IFN-gamma with higher IL-10 and less IL-12 production than heparin-untreated DCs. Heparin-treated DCs are more potent in priming allogeneic and autologous CD4+ T cells to proliferate and to produce both type 1 and type 2 cytokines. The results of our study show that CD1a+ DCs can be prepared from monocytes ex vivo without using xenogeneic serum and may be used for immunotherapy.
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PMID:Heparin induces differentiation of CD1a+ dendritic cells from monocytes: phenotypic and functional characterization. 1180 47

This study was to establish the method of purifying heat shock protein GP96 from K562 cells and explore the differentiation and function of human DC influenced by heat shock prolein (HSP). Using ammonium sulfate precipitation, conA-sepharose affinity chromatography and DEAE-sephacel anion exchange chromatography GP96 from K562 cells lysate was isolated and purified. The identification of the purified protein was controlled by Western blot with anti-human GP96 IgG. Human dendritic cell derived from peripheral blood mononuclear cell were cultured with purified GP96. The phenotype changes of DC were analyzed by flow cytometry and MLR was detected by MTT. The results showed that 60-80 microg GP96 was purified successfully from 1 x 10(10) K562 cells. DC stimulated with HSP-GP96 had higher expression rates of CD83, CD86, HLA-DR and lower expression rates of CD1a and had stronger ability to induce T cells proliferation. It is concluded that heat shock protein GP96 can be isolated and purified from K562 cells and could induce maturation of dendritic cell. HSP-DC vaccine show stronger ability to induce T cell proliferation than DC.
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PMID:[Differentiation and function of human dendritic cells influenced by heat shock protein gp96 purified from K562 cells]. 1549 22

CD1a protein binds sulfatide (3-O-sulfo-beta-D-galactosylceramide) to form an antigen complex that interacts with T cell receptors and activates T cells. To assess the role of the position of the sulfate in T cell activation, the synthesis of three beta-D-galactosylceramides, variously bearing a sulfate at position 2, 4, or 6 of galactose, has been planned and carried out. The compounds were synthesized by an orthogonal sulfation strategy from a common beta-D-galactosylceramide scaffold, which was in turn obtained through an efficient glycosylation reaction between a fully orthogonally protected galactosyl imidate and 3-O-benzoylazidosphingosine. Immunological evaluation of the three sulfated compounds in CD1a-mediated T cell activation, in comparison with natural sulfatide, provided evidence of the influence of the sulfate position in the recognition event between the antigen, the CD1 protein and the T cell receptor.
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PMID:Synthesis of sulfated galactocerebrosides from an orthogonal beta-D-galactosylceramide scaffold for the study of CD1-antigen interactions. 1663 81

In the induction phase of allergic contact hypersensitivity, dendritic cells (DCs), including Langerhans cells (LCs) present in epidermis, can trigger an efficient T cell response once they have matured in response to an allergen. Upon maturation, DCs have been shown to induce expression of several surface molecules and the up-regulation of cytokine production. We have previously shown that THP-1 cells, human acute monocytic leukemia cell line, can discriminate between allergens and irritants by measuring expression of surface markers, CD86 and CD54, following chemical exposure. At the same time, we have also reported that augmented expression of HLA and CD80, and production of IL-1beta were up-regulated in THP-1 cells when treated with an allergen, 2,4-dinitrochlorobenzene (DNCB). In the present study, we first evaluated whether THP-1 cells induced the phenotypic changes and the production of cytokines, which are observed in the process of DC maturation, when treated with two known allergens, DNCB and nickel sulfate (NiSO(4)), and one irritant (sodium lauryl sulfate (SLS)). Exposure to DNCB and NiSO(4) induced significant augmentation of CD40 and CD83 expression as well as CD86 and CD54. Also, TNF-alpha and IL-8 secretion were markedly induced by DNCB and NiSO(4) in a dose-dependent manner. In addition, DNCB and NiSO(4) augmented CD1a expression and production of IL-6, respectively. On the contrary, SLS did not change any of these markers. We then evaluated a series of chemicals, including six known allergens (e.g., hydroquinone (HQ)) and two non-allergens (e.g., methyl paraben (MP)), in order to investigate the potential increase of CD86, CD54, CD40, and CD83 expression on THP-1 cells, and production of TNF-alpha and IL-8. Indeed, all tested allergens, except eugenol (EU), caused significant increased changes in at least four of the analyzed six markers, while non-allergens did not induce any changes. EU significantly augmented CD86, CD54 and CD40 expression. These results revealed that the wide variety of responses to allergens in THP-1 cells may emulate allergen-induced maturation processes of DCs. It is suggested that THP-1 cells, which could develop several DC-like properties, are suitable for identifying sensitizing potential of chemicals.
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PMID:Phenotypic alterations and cytokine production in THP-1 cells in response to allergens. 1711 22

IL-4 induces the differentiation of monocytes toward dendritic cells (DCs). The activity of many cytokines is modulated by glycosaminoglycans (GAGs). In this study, we explored the effect of GAGs on the IL-4-induced differentiation of monocytes toward DCs. IL-4 dose-dependently up-regulated the expression of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), CD80, CD206, and CD1a. Monocytes stained positive with Abs against heparan sulfate (HS) and chondroitin sulfate (CS) B (CSB; dermatan sulfate), but not with Abs that recognize CSA, CSC, and CSE. Inhibition of sulfation of monocyte/DC cell surface GAGs by sodium chlorate reduced the reactivity of sulfate-recognizing single-chain Abs. This correlated with hampered IL-4-induced DC differentiation as evidenced by lower expression of DC-SIGN and CD1a and a decreased DC-induced PBL proliferation, suggesting that sulfated monocyte cell surface GAGs support IL-4 activity. Furthermore, removal of cell surface chondroitin sulfates by chondroitinase ABC strongly impaired IL-4-induced STAT6 phosphorylation, whereas removal of HS by heparinase III had only a weak inhibitory effect. IL-4 bound to heparin and CSB, but not to HS, CSA, CSC, CSD, and CSE. Binding of IL-4 required iduronic acid, an N-sulfate group (heparin) and specific O sulfates (CSB and heparin). Together, these data demonstrate that monocyte cell surface chondroitin sulfates play an important role in the IL-4-driven differentiation of monocytes into DCs.
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PMID:Monocyte cell surface glycosaminoglycans positively modulate IL-4-induced differentiation toward dendritic cells. 1832 73

Dendritic cells (DC) are highly specialized antigen-presenting cells (APC) located in many non-lymphoid tissues and a specialized form of DC-the Langerhans cell (LC)-is found in the skin. The functionality of LC as APC is crucial for the induction of an allergic contact dermatitis. For a long time LC research has been hampered by the limiting numbers of functionally active LC that could be isolated from human skin. The addition of GM-CSF and IL-4 to the non-adherent fraction of mononuclear cells from peripheral blood generated a large amount of CD1a(+) HLA-DR(+) DC. These in vitro-generated DC exhibited the morphology, phenotype and autologous T-lymphocyte stimulating capacity of the human DC/LC system. We had tested phenotypical alterations of in vitro-generated DC under the influence of subtoxic concentrations of different chemicals and contact sensitizers. In vitro stimulation with the contact sensitizers urushiol, primin, C10-and C11-primin analogues, alantolactone, isoalantolactone and NiSO(4) resulted in a decrease of HLA-DR expression on the surface of these cells if the incubation period did not exceed 3 hr. Incubation with irritants like sodium lauryl sulfate (SLS) and benzalkonium chloride did not change or increase the HLA-DR surface expression under these conditions. With regard to the adhesion molecule ICAM-1, there was no clear difference between irritants and contact sensitizers. But based on the alteration of HLA-DR expression of dendritic cells under short-term exposure conditions, there was a clear-cut difference between irritants and contact sensitizers. In summary, this system can be used to discriminate between contact sensitizers and irritants.
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PMID:In vitro model for contact sensitization: I. Stimulatory capacities of human blood-derived dendritic cells and their phenotypical alterations in the presence of contact sensitizers. 2065 59


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