不同类型钙通道阻滞剂对小鼠变应性接触性皮炎及表皮郎格罕细胞的影响

为了探讨钙通道阻滞剂（ＣＣＢｓ）对迟发型超敏反应（ＤＨＲ）的作用及其机制，我们观察了三类８种ＣＣＢｓ对小鼠变应性接触性皮炎（ＡＣＤ）及表皮郎格罕细胞（ＬＣｓ）的影响。结果发现Ⅰ类ＣＣＢｓ异搏定、硫氮酮，Ⅱ类ＣＣＢｓ尼莫地平、尼群地平及Ⅲ类ＣＣＢｓ脑益嗪在抑制ＤＨＲ的同时，亦减少表皮ＬＣｓ数。提示上述药物可通过降低表皮ＬＣｓ数而抑制ＤＨＲ。另外３种Ⅱ类ＣＣＢｓ心痛定、尼卡地平及络活喜亦显著抑制小鼠ＡＣＤ，但并未显示同时减少表皮ＬＣｓ数，提示ＣＣＢｓ对ＡＣＤ抑制作用的机理可能因药而异。     

不同类型钙通道阻滞剂对小鼠变应性接触性皮炎及表皮郎格 …

为了探讨钙通道阻滞剂（ＣＣＢｓ）对迟发型超敏反应（ＤＨＲ）的作用及其机制，我们观察了三类８种ＣＣＢｓ对小鼠变应性接触性皮炎（ＡＣＤ）及表皮郎格罕细胞（ＬＣｓ）影响。结果发现Ⅰ类ＣＣＢｓ异搏定、硫的氮酮，Ⅱ类ＣＣＢｓ尼莫地平、尼群地平及Ⅲ类ＣＣＢｓ佃嗪在抑制ＤＨＲ的同时，亦减少表皮ＬＣｓ数。提示上述药物可通过降低表皮ＬＣ数而抑制ＤＨＲ。另外３种Ⅱ类ＣＣＢｓ心痛定、尼卡地平及络活喜亦显著抑制小鼠ＡＣ     

赛庚啶对人血糖、胰岛素及胰高糖素水平的影响

赛庚啶对人血糖、胰岛素及胰高糖素水平的影响张谊之，杨华，邓尚平，魏松全近年来，国外较多报道赛庚啶（ＣＰＨ）能引起家兔胰岛β细胞结构和功能的改变，使胰岛素（ＩＮＳ）分泌减少。但ＣＰＨ对人血糖、ＩＮＳ及胰高糖素（ＧＤＬ）水平的影响国内尚无报道。为此，我们...     

1,25（OH）2维生素D3对小鼠郎格罕细胞和接触变态反应的影响

研究了不同浓度的１，２５（ＯＨ）２维生素Ｄ（ＶＤ３）外涂对小鼠表皮郎格罕细胞（ＬＣ）的影响及对接触变态反应（ＣＨＳ）的局部和系统抑制作用。结果表明随着１，２５（ＯＨ））２ＶＤ３浓度的增加，ＬＣ树枝状减少，呈现卵圆或圆形细胞并且细胞数量下降。局部使用治疗剂量的１，２５（ＯＨ）２ＶＤ３能直接抑制小鼠的ＣＨＳ。并且，接受此种处理的小鼠脾细胞后，受体小鼠的ＣＨＳ亦同样抑制。这提示与诱导体内抑制性淋巴细胞的     

红斑狼疮皮损中浸润细胞免疫表型和角质形成细胞HLA-DR抗原表达的研究

应用抗ＨＬＡＤＲ、ＣＤ３、ＣＤ４、ＣＤ８、ＣＤ２０的单克隆抗体和ｓｔｒｅｐｔｒａｖｉｄｉｎｐｅｒｏｘｉｄａｓｅｓｔａｉｎｉｎｇ（ＳＰ）技术对１０名正常人皮肤,１６例ＳＬＥ皮损和１９例ＤＬＥ皮损进行了免疫组化研究。观察到正常人皮肤角质形成细胞未见ＨＬＡＤＲ抗原表达,而ＳＬＥ（６／１６）,ＤＬＥ（８／１９）皮损处角质形成细胞可以表达ＨＬＡＤＲ抗原。在ＳＬＥ、ＤＬＥ真皮内浸润细胞主要为Ｔ淋巴细胞（ＣＤ３＋浸润细胞）,且以ＴＨ细胞（ＣＤ４＋浸润细胞）占优势。另外,还发现在两种ＬＥ表皮角质形成细胞表达ＨＬＡＤＲ抗原处,真皮内可见ＣＤ３＋浸润细胞和激活的Ｔ淋巴细胞（ＨＬＡＤＲ＋浸润细胞）。讨论了ＬＥ皮损角质形成细胞ＨＬＡＤＲ抗原表达及其与病损内浸润细胞免疫表型的关系。ＬＥ皮损处ＨＬＡＤＲ＋角质形成细胞可能具有抗原递呈作用,而角质形成细胞异常表达ＨＬＡＤＲ抗原则可能与真皮内浸润单个核细胞或淋巴细胞释放的ＩＦＮα,ＴＮＦγ等有关。     

阿化斯丁治疗40例慢性荨麻疹

阿化斯丁（ａｃｒｉｖａｓｔｉｎｅ）商品名新敏乐（Ｓｅｍｐｒｅｘ），为新型的第二代Ｈ１受体拮抗剂。我们最近采用英国葛兰素威康集团公司研制的新敏乐胶囊，对４０例慢性荨麻疹患者进行了治疗，结果如下。一、病例资料１９９４年９月至１９９５年４月期间在我所门诊就诊的慢性荨麻疹患者４０例。其中男２０例，女２０例。年龄为１２～６５岁，平均年龄３０．５岁。病程为２个月至７年，多在２年之内。发病原因、诱因不很明确。其中有２３例患者有明确的使用其它抗组胺药物或皮质类固醇激素史。抗组胺药包括有扑尔敏、赛庚啶、特非那丁、…     

鱼鳞病患者鳞屑、皮肤和血液的胆固醇和胆固醇硫酸酯分析

目的：探讨脂质与鳞屑性疾病的关系。方法：用气相质谱方法对性联隐性鱼鳞病（ＲＸＬＩ）、寻常性鱼鳞病（ＩＶ）各５例和５例正常对照组的鳞屑、表皮、真皮和血液中的胆固醇硫酸酯（ＣＳ）和胆固醇（ＣＨ）进行了定量分析。结果：鳞屑中ＲＸＬＩ组ＣＳ含量显著高于ＩＶ和正常对照组，ＣＨ和ＣＨ／ＣＳ显著低于其他二组。在表皮、真皮和血液中，ＲＸＬＩ组ＣＳ含量显著增高，而ＣＨ含量无明显变化，ＣＨ／ＣＳ下降。结论：ＲＸＬＩ的鳞屑产生与ＣＳ积聚及ＣＨ／ＣＳ下降有关，而ＩＶ的发病则与ＣＳ和ＣＨ无关。     

系统性红斑狼疮患者外周血单一核细胞CD23的表达

为了揭示Ｂ细胞中ＣＤ２３的表达与ＳＬＥ发生发展的关系及在ＳＬＥ发病机理中可能的作用，我们应用ＡＢＣ免疫组化法和斑点核酸杂交技术对ＳＬＥ患者外周血单一核细胞（ＰＢＭＣ）ＣＤ２３蛋白和ｍＲＮＡ表达进行了检测。结果显示：３０例ＳＬＥ患者ＰＢＭＣＣＤ２３蛋白表达显著增高（Ｐ＜０．０１），且与疾病活动呈正相关关系（ｒｓ＝０．３８１４，Ｐ＜０．０５）；具有不同ＡＮＡ、抗ｄｓＤＮＡ抗体水平，有无伴肾损、脑损的ＳＬＥ患者，ＰＢＭＣＣＤ２３表达均无显著性差异（Ｐ均＞０．０５）；单纯使用皮质类固醇激素治疗或和其它免疫抑制剂联合治疗的ＳＬＥ患者，ＰＢＭＣＣＤ２３表达亦无显著性差异（Ｐ＞０．０５）。２０例ＳＬＥ患者ＰＢＭＣＣＤ２３ｍＲＮＡ表达较正常人显著增高（Ｐ＜０．０１）。经治疗病情稳定后，ＣＤ２３蛋白和ｍＲＮＡ表达均降至正常（Ｐ均＞０．０５）。提示在ＳＬＥ活动期Ｂ细胞高度激活、增殖并大量表达ＣＤ２３，且该种表达与ＡＮＡ、抗ｄｓＤＮＡ抗体产生水平无直接关系     

大疱性系统性红斑狼疮的皮肤基底膜带相关抗原

免疫印迹和盐裂皮肤间接免疫荧光检测 ５例大疱性系统红斑狼疮（ＢＳＬＥ）血清，对照为 ５例获得性大疤性表皮松解症（ＥＢＡ）、２０例类天疱疮（ＢＰ）、２０例ＳＬＥ和１０例正常人血清。结果表明，３例（３／５）ＢＳＬＥ血清结合盐裂皮肤真皮侧和真皮提取物中２９０ ０００抗原，其中２例ＢＳＬＥ血清也结合表皮提取物中 １６５ ０００抗原，结果与 ＥＢＡ和部分ＢＰ血清相同。ＳＬＥ血清未结合 ２９０ ０００和 １６５ ０００抗原。提示ＢＳＬＥ血清中存在ＥＢＡ和ＢＰ抗体，推测ＥＢＡ和ＢＰ抗原可能是ＢＳＬＥ的皮肤基底膜带相关抗原。     

特非那丁与雷尼替丁联合应用治疗慢性荨麻疹32例

特非那丁与雷尼替丁联合应用治疗慢性荨麻疹３２例渐怀平，刘侃玉山东枣庄市薛城区人民医院皮肤科（邮政编码２７７０００）３２例中男１２例，女２０例，年龄１８～４８岁，病程３月～７年。发病原因不明，均用过扑尔敏、赛庚啶、息斯敏等疗效不佳。治疗方法治疗组３２例...     

Down-regulation of Langerhans cell protein kinase C-β isoenzyme expression in inflammatory and hyperplastic dermatoses

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. Ca²⁺-dependent PKC activity, PKC-β protein and epidermal Langerhans cell (LC) PKC-β 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-α and PKC-β 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-α and PKC-β, and the LC marker CDla, using an immunoperoxidase technique and specific monoclonal antibodies. Double-labelling studies, in normal skin, revealed co-expression of PKC-β and CDla by epidermal LCs. Analysis of the number of PKC-^β+ and CDl^a+ epidermal LCs, in diseased compared with normal skin, revealed three categories: (i) in psoriasis and CTCL. the PKC-^β+ epidermal LC number was significantly reduced, whereas the CDl^a+ epidermal LC number was unchanged; (ii) in allergic and irritant contact dermatitis, both PKC-β+ and CDla⁺ epidermal LCs were significantly reduced in number; and (iii) in atopic dermatitis, the PKC-β⁺ epidermal LC number was normal, and CDla⁺ epidermal LCs were significantly increased in number. Moreover, the ratio of epidermal LC PKC⁺/CDla⁺ was reduced in all the dermatoses studied, suggesting activation of PKC-β, with subsequent down-regulation. Within the dermis, increased PKC-β 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 FKC-β occurs in a variety of inflammatory and hyperplastic skin disorders, and is not unique to psoriasis, and (iii the pattern of epidermal LC PKC-β and CDla expression varies among the diseases studied. In mice, PKC activation induces LC migration. Thus, down-regulation of epidermal LC PKC-β associated with reduced CDla⁺ epidermal LCs in allergic and irritant contact dermatitis suggests that PK.C-β may transduce the signal for migration of LCs from human epidermis.     

CD70-CD27 interaction augments CD8+ T-cell activation by human epidermal Langerhans cells

Human cutaneous dendritic cells (DCs) from epidermal and dermal compartments exhibit functional differences in their induction of CD4+ T-cell and humoral immune responses; however, differences in the regulation of memory CD8+ T-cell responses by human skin DCs remain poorly characterized. We tested the capacity of human Langerhans cells (LCs) and dermal dendritic cells (DDCs) to induce antigen-specific cytokine production and proliferation of memory CD8+ cells. Although tumor necrosis factor-α-matured human DCs from both epidermal and dermal compartments showed efficient potential to activate CD8+ cells, LCs were constitutively more efficient than DDCs in cross-presenting CD8+ epitopes, as well as direct presentation of viral antigen to Epstein-Barr virus-specific CD8+ T cells. LCs showed greater expression of CD70, and blockade of CD70-CD27 signaling demonstrated that superiority of CD8+ activation by epidermal LC is CD70 dependent. This CD70-related activation of CD8+ cells by LCs denotes a central role of LCs in CD8+ immunity in skin, and suggests that regulation of LC CD70 expression is important in enhancing immunity against cutaneous epithelial pathogens and cancer.     

Immunohistochemical evidence of skin immune system involvement in vulvar lichen sclerosus et atrophicus

Biopsies taken from vulvar lesions in 12 women affected by vulvar lichen sclerosus et atrophicus (LSA) have been processed for immunohistological study. Activated (HLA-Dr+) T cells, associated with CD1a+ accessory cells, were found in the dermis in all cases, with architectural patterns varying in relation to the histological phase (early, well developed, old) of the lesion. Interestingly, the number of epidermal CD1a+ Langerhans cells (LCs) was increased in all cases, without any correlation with the amount of the dermal infiltrate and with the histological phase of the lesions. In fact, also in old lesions the number of epidermal CD1a+ LCs was increased, and the sparse dermal lymphoid cells showed a persistent HLA-Dr antigen expression. These data, indicating the persistent activation of epidermal antigen-presenting cells and lymphoid cells in all the evolutive phases of vulvar LSA, suggest a possible involvement of the skin immune system in the pathogenesis of LSA.     

Cytochemical and Ultrastructural Studies of the Langerhans' Cells

Abstract: In the guinea pig, experimental allergic contact dermatitis (ACD) And primary irritant contact dermatitis (PICD) were induced with different concentrations of dinitrochlorobenzene (DNCB). The epidermal Langerhans' cells (LCs) were observed sequentially by both adenosine triphosphatase (ATPase) and electron microscopy. Light microscopically, in ACD, the density and dendritic processes of LC decreased markedly within 12 h after antigen challenge. Almost no recognization LCs could be seen within 2 to 5 days. Later, LCs began to repopulale in the epidermis. Within 14 days, the density and shape of the LCs returned to normal. On the contrary, LCs changed more rapidly in PICD. The dendritic processes of LC decreased within 2 h and cell density decreased dramatically within 6 h after DNCB application. LCs also repopulated more rapidly in the epidermis. Electron microscopically, in ACD, we observed that lymphocyte-like cells apposed to LCs; LCs were activated and damaged; however, in PICD, we found neither the apposition of lymphocyte-like cells to LCs, nor the activation of LCs. LCs play an important role in the convalescence phase as well as in the early and later phases of contact allergic reaction.     

Effects of topical corticosteroid therapy on Langerhans cell antigen presenting function in human skin

We have investigated the mechanisms by which topical corticosteroids modulate cutaneous immune reactions in man. Volunteers applied clobetasone butyrate 0.05% (Eumovate; EV), betamethasone valerate 0.1% (Betnovate; BV), clobetasol propionate 0.05% (Dermovate; DV), and control vehicles twice daily to forearm skin for 7 days. Steroid therapy significantly decreased the number of HLA-DR/T6 (CD1a) positive Langerhans cells (LCs) per mm2 in suction blister-derived epidermal sheets, expressed as a mean percentage of controls, as follows: EV 69.2%; BV 67.3%; DV 37.8%. LC antigen presenting capacity was determined in the allogeneic and autologous epidermal cell-lymphocyte reactions. The LC-dependent allostimulatory capacity of epidermal cells, expressed as a mean percentage of controls, was also significantly reduced by steroid therapy: EV 45.1%; BV 41.9%; DV 23.4%. Following therapy with clobetasol propionate 0.05%, the capacity of epidermal cells to present tetanus toxoid to, and to augment concanavalin A mediated lymphocyte stimulation of, autologous lymphocytes was reduced to 33.6% and 19.7% respectively of controls. Depression of epidermal cell allostimulatory capacity was not the result of a steroid-induced decrease in the production of epidermal cell-derived thymocyte activating factor (ETAF)/interleukin 1 by keratinocytes, since it could not be reversed by addition of exogenous interleukin 1. Indomethacin, added to block any potential prostaglandin synthesis during the culture period, did not restore the allostimulatory capacity of epidermal cells from steroid-treated sites. Addition of epidermal cells from DV-treated sites depressed the capacity of control epidermal cells to stimulate lymphocytes in the allogeneic epidermal-lymphocyte reaction. Our results demonstrate that the anti-inflammatory action of topical corticosteroids in man is associated not only with a reduction in the number of HLA-DR/T6 positive LCs, but also with a marked decrease in Langerhans cell-dependent T lymphocyte activation. The effects of the different steroids on both of these parameters correlated with their potency as determined in the standard occlusive vasoconstrictor assay. Topical corticosteroids are widely used for the treatment of inflammatory skin disorders, and inhibit not only the elicitation phase, but also the induction phase, of allergic contact dermatitis reactions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Langerhans cells in various benign and malignant pigment-cell lesions of the skin

Summary We used immunohistochemistry to study Langerhans cells (LCs) and the composition of the dermal inflammatory infiltrate both in normal skin and in biopsies from various benign and malignant pigment-cell lesions. In normal skin and most benign pigment-cell lesions, epidermal LCs are regularly distributed. OKT₆-Positive cells outnumber the OKIa-positive cells. The inconspicuous dermal infiltrate studied in these biopsies was composed of helper and suppressor/cytotoxic T cells and some dermal LCs. More epidermal LCs with an abnormal cytologic presentation were found in a halo naevus and in the radial growth part of primary malignant melanomas. This finding was associated with a dermal infiltrate composed of suppressor/cytotoxic T cells, suggesting a defense mechanism of the host towards abnormal melanocytes. Epidermal LCs were rare in the central part of the biopsies which showed a primary malignant melanoma in its vertical growth. A dermal inflammatory infiltrate was absent in that area. These findings are interpreted as the morphologic expression of a damaged immune system.F. Facchetti is on leave from Istituto di Anatomia Patologica, Spedali Civili di Brescia, Brescia, Italy     

Turnover and kinetics of epidermal langerhans cells and their dendritic precursor cells in experimental contact dermatitis

The numerical density of epidermal Langerhans cells (LCs) in contact sensitivity and toxic contact dermatitis is still a matter of controvery, mainly due to changes in the phenotypic markers of this antigen-presenting cell during the skin reactions. Since the electron microscopic detection of Birbeck granules is the most reliable marker for the identification of normal and pathologically altered LCs, we performed an ultrastructural-morphometric time-course analysis to evaluate their epidermal turnover in the earskin of BALB/c mice after painting the ears with the hapten 2,4-dinitrofluorobenzene and the irritant croton oil. The counts revealed degeneration and depletion of epidermal LCs in both allergic and toxic dermatitis. In contrast, a slightly increased number of activated epidermal LCs was found during contact sensitization. All experimental procedures resulted in an enhanced immigration of so-called indeterminate dendritic cells which also became ultrastructurally activated and often showed Birbeck granule-like formations at their cell membrane. Immunohistochemistry with the monoclonal antibody 4F7, a new marker for dendritic precursor cells of LCs, demonstrated a significant increase in these accessory cells in the epidermis. Our results indicate that contact sensitivity and toxic skin reactions are characterized by complex but distinct changes in the turnover, kinetics and cellular properties of epidermal LCs and their dendritic precursor cells. Received: 16 March 1995     

Selective 5-lipoxygenase expression in Langerhans cells and impaired dendritic cell migration in 5-LO-deficient mice reveal leukotriene action in skin

5-Lipoxygenase (5-LO) catalyzes the initial steps in the formation of leukotrienes (LTs), which are implicated in immune reactions. Recently, it was shown that FITC-triggered epidermal Langerhans cell (LC) emigration to draining lymph nodes (LNs) is impaired in LTC4 export pump (multidrug resistance-associated protein 1)-deficient mice. Here, we sought genetic evidence for a role of endogenous LTs in dendritic cell function through the study of 5-LO-deficient mice. Though DC numbers in skin, spleen, and peripheral LNs were similar in both 5-LO-deficient and wild-type (WT) mice, DC homing from skin to draining LNs induced by FITC was reduced by 75% in 5-LO-deficient mice. Moreover, in WT mice, all epidermal LCs, dermal langerin+ LCs, and subsets of dermal macrophages and langerin+ LCs in T-cell areas of skin-draining LNs markedly expressed 5-LO. However, the enzyme was noticeably absent in all DC subsets of the dermis, thymus, spleen, Peyer's patches, mesenteric LNs, and mucosal surfaces of lung and intestine. As all epidermal cells other than LCs lacked 5-LO and because differentiation and activation of DCs generated from 5-LO-deficient mice in vitro were normal, these data support a selective role of endogenous LTs in DC homing following skin sensitization.