银屑病患者粒-单核巨噬细胞集落刺激因子表达的研究

目的 探讨脓疱性银屑病和寻常性银屑病患者皮损组织及外周血粒-单核巨噬细胞集落刺激因子（GM-CSF）表达的变化。方法 免疫组化法和双抗体夹心酶联免疫吸附法（ELISA）分别检测脓疱性银屑病和寻常性银屑病患者皮损组织和外周血中GM-CSF表达水平,并与正常人进行比较。结果 与正常人对照组相比,脓疱性银屑病组和寻常性银屑病组皮损组织中GM-CSF表达均增高（P < 0.01）,且脓疱性银屑病组皮损组织中GM-CSF表达高于寻常性银屑病组（P < 0.01）。与正常人对照组相比,脓疱性银屑病组和寻常性银屑病组外周血中GM-CSF含量均升高（P < 0.01）,且脓疱性银屑病组外周血中GM-CSF水平高于寻常性银屑病组（P < 0.01）。结论 GM-CSF可能参与银屑病的发病。     

Langerhans cells in the physiopathology of atopic dermatitis

INTRODUCTION. Atopic dermatitis (AD), allergic rhino-conjunctivities and allergic asthma constitute the classical triad of atopic diathesis attended, in many cases, by high serum IgE levels. While the pathophysiology of IgE-mediated allergic respiratory diseases is now better understood, the pathophysiological significance of atopic phenomena in the genesis and control of AD is still far from being clear. Numerous clinical and laboratory data point to a pathophysiological relation between IgE-mediated reactions and AD, but no one yet knows by which mechanism this interaction takes place. Some recent studies suggest that Langerhans cells might well be the missing link. THE LANGERHANS CELLS. Langerhans cells (LC) are dendritic epidermal cells originating in the bone marrow and supposedly belonging to the monocyte lineage. Their circulating precursors, the mechanism of their migration into the epidermis and their relationship with other dendritic cells, such as the interdigitating follicular cells, are controverted. LC express numerous surface markers, such as class I and II HLA, CD1a, CD4 and receptors for complement and IgE Fc fragments. Under normal conditions, LC do not express IgE receptors. Ultrastructurally, LC are characterized by the presence of Birbeck granules in their cytoplasm. Among the presumed functions of LC in the skin, the best documented is the presentation of antigens to T lymphocytes in allergic contact dermatitis. LANGERHANS CELLS IN ATOPIC DERMATITIS. Quantitative studies. Modern immunohistological methods based on the reactivity of monoclonal anti-CD1a antibodies have given results that are sometimes conflicting due to differences in the quantification techniques utilized. However, morphometric enumeration of LC on cryostat sections have shown that their number is about the same in AD and in normal skin. PRESENCE OF IgE BEARING LANGERHANS CELLS IN ATOPIC DERMATITIS. The presence of IgE molecules on the LC surface has been demonstrated in subjects with AD. It must be noted that in atopic subjects IgE bearing Lc are only found in patients with high serum IgE levels. They are absent in asthma patients without eczema, irrespective of their serum IgE levels. Daily applications of corticosteroids on AD lesions result in a decrease of anti-IgE markers on LC after one week and in their complete disappearance after 2 weeks. IN ATOPIC DERMATITIS LANGERHANS CELLS EXPRESS A RECEPTOR SPECIFIC TO Fc FRAGMENTS OF IgE. The exact nature of the receptor for IgE expressed in situ in AD patients is still conjectural. Some authors have been able to demonstrate that the binding of IgE molecules by LC isolated from the skin of atopic patients is inhibited by a monoclonal antibody directed against the low affinity receptor (Fc epsilon R2) of eosinophils and macrophages. This strongly suggests that certain factors induce the expression by LC of an Fc epsilon R2 receptor. IN VITRO INDUCTION OF IgE RECEPTORS ON NORMAL LANGERHANS CELLS...     

Interleukin-3 in cooperation with transforming growth factor beta induces granulocyte macrophage colony stimulating factor independent differentiation of human CD34+ hematopoietic progenitor cells into dendritic cells with features of Langerhans cells

Recently, we have reported that M-CSF in cooperation with TGF-beta1 can induce Langerhans cell (LC) development from hematopoietic progenitor cells (HPCs) without GM-CSF. In the present study, we examined whether TGF-beta1 changes the differentiation of HPCs induced by IL-3 towards LC development. We cultured HPCs in a serum-free medium in the presence of IL-3 and a combination cytokines including Flt3L, SCF, and TNF-alpha with or without TGF-beta1. DCs induced by the IL-3 culture (IL-3 DCs) did not significantly differ from those induced by the GM-CSF culture (GM-CSF DCs). Namely, both expressed CDla, F-cadherin, and Langerin in the presence of TGF-beta1 and stimulated allogeneic T cells at a similar magnitude. In contrast to GM-CSF DCs, IL-3 DCs lacked the expression of Birbeck granules (BGs) in spite of their expression of Langerin. When we compared the expression of Langerin between these two DCs, however, it became clear that both Langerin protein and mRNA were significantly lower in IL-3 DCs than in GM-CSF DCs. These studies again demonstrated the ability of TGF-beta1 to polarize the differentiation of HPCs induced by IL-3 towards LC development, although IL-3 DCs were unable to form BGs partly because of their poor ability to induce Langerin.     

Contact allergy to Dermatophagoides in atopic dermatitis patients and healthy subjects

To compare different house-dust-mite-derived allergenic materials and to correlate the presence of IgE LO Dermatophagoides with patch test results, 313 atopic dermatitis (AD) patients and 100 healthy volunteers (HV) underwent patch tests with: Dermatophagoides Pteronyssimus (DPT) lyophilized purified alpha fraction in buffered saline/glycerol 50% and or in petrolatum (Bayropharm); 540% DPT and 50% Dermatophagoides farinae (DF) whole bodies in petrolatum and petrolatum oil (Allergopharma-Bracco); DPT and DF whole bodies in petrolatum and petrolatum oil (Lofarma). We found 39% positive reactions among AD subjects and 13% in HV The presence of serum-specific IgE did not influence the patch test results. with of AD patch-lest-positive patients and 5 of 13 HV respectively, showed a positive prick less and or RAST lo Dermatophagoides. Similar sensitization rates were observed with the allergenic material from Bayropharm (54% positivities) and Allergopharma-Bracco (51% positivities), whereas the preparations from Lofarma gave a 20% response rate.     

Toxic epidermal necrolysis treated with cyclosporin and granulocyte colony stimulating factor

A patient developed toxic epidermal necrolysis while on carbamazepine, 80% of her skin surface being involved. She also developed a pancytopenia with a neutropenia of 0.77×10⁹ (normal range 27.5× 10⁹/1), but was treated with cyclosporin and granulocyte colony stimulating factor and made a full recovery.     

The action of levamisole on thymodependent rosettes in normal and atopic subjects]

Thymo-derived E-rosettes and fast E-rosettes have been determined in 26 normal and 17 atopic patients. The effect of levamisole in vitro has been studied by adjunction in the cell suspension at a concentration of 100 gamma/ml. In normal and atopic subjects the E-rosettes are not modified by levamisole. Fast E-rosettes are significantly increased by levamisole in normal but not in atopic patients. These results support the hypothesis of a functional deficiency of T-lymphocytes in atopy; they are correlated by the failure of treatment of atopic dermatitis by levamisole.     

Langerhans cells in normal human skin capillaries

Cells with Langerhans granules are reported for the first time in normal human skin capillaries.     

Mitotic activities of normal epidermal Langerhans cells

We have previously reported a sequence of events which occurs during the recovery phase of the murine epidermal Langerhans cells (ELCs) after ultraviolet-B irradiation. We found that an ATPase-positive round cell divides, dendrites are gradually formed, and paired dendritic cells are eventually separated as the post-irradiation time elapses. We wondered if a series of events similar to this might occur in the normal murine epidermis without irradiation. In this study, we could identify exactly the same phases of the ELC mitotic cycle in normal mouse ear skin.     

Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin

Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out at the site of each biopsy. After fixation and plastic embedding, the biopsies were cut into 2 μm serial sections. Ten sections, 30 μm apart, from each biopsy were examined and stained alternately with either toluidine blue or Giemsa stain and mast cell profile numbers were determined. The study yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly increased number of mast cell profiles per millimetre squared was found in specimens from the neck, (3) staining with toluidine blue yielded a lower number of mast cell profiles than Giemsa staining, (4) the use of Carnoy’s fixative resulted in a lower mast cell profile count than the use of formaldehyde, and (5) there was no statistically significant correlation between the clinical score and the number of mast cell profiles per millimetre squared. Using stereological techniques, this study indicated that mast cells might participate in the inflammatory process in skin leading to atopic dermatitis. Received: 17 April 1996     

Measurement of phosphoinositide-specific phospholipase C activity in mononuclear leucocytes from atopic and normal subjects

The intracellular inositol pathway is an important route for cell activation and relies on the stimulation of membrane-bound phosphoinositide-specific phospholipase C (PLC). Previously we have shown abnormalities of inositol metabolism in mononuclear cells (MNL) in atopic dermatitis (AD) using an indirect method. We now describe a direct method of measuring PLC activity in membrane and cytosol preparations of MNL in AD. We compare PLC activity in AD with that in normal controls and examine the effect of substrate concentration and nucleotide stimulation on the system. Our findings show increased membrane-bound PLC activity in AD compared with normal controls. Non-specific stimulation of AD PLC activity by nucleotides suggests that the enzyme of atopics is more sensitive to substrate-driven activity than that of non-atopics.     

Distribution of ATPase-positive Langerhans cells in normal adult human skin

The distribution of ATPase-positive Langerhans cells (LC) was investigated in 117 specimens of normal adult human skin and mucosa taken from different areas of the body. Although there were significant variations in the numbers of LC in each area examined, skin from the face and neck contained the highest density of cells (976 +/- 30.93/mm2). The densities of LC in trunk skin (740 +/- 28.97/mm2), scalp (693 +/- 69.56/mm2) and arm or leg skin (640 +/- 40.95/mm2) were similar. Buccal mucosa had significantly fewer LC (567 +/- 42.94/mm2) than trunk skin, and sacrococcyx skin and palm and sole skin displayed the smallest number of these cells (267 +/- 56.14/mm2 and, 189 +/- 19.15/mm2 respectively). No ATPase-positive LC were detected in the centre of two corneal specimens.     

Effect of glucocorticoids and gamma radiation on epidermal Langerhans cells

The effect of 750 rads of gamma radiation on the rate of return of epidermal Langerhans cells (LC) following suppressive doses of topical glucorticoids was studied in guinea pigs. Gamma radiation alone had no effect on the LC as assessed by staining for cell membrane ATPase activity and Ia antigen. It did, however, delay the expected return of Ia but not ATPase surface markers on the LC after perturbation with glucocorticoids. The delayed return of surface Ia antigen is possibly related to a radiation-induced defect in the production of a required lymphokine and/or in intracellular Ia transport. Although our data do not rule out a cytolytic effect of steroids on the LC, they do strongly suggest that, at least in part, glucocorticoids act on the LC by altering cell surface characteristics.