PHOSPHODIESTERASE STUDIES IN ATOPIC DERMATITIS

特应性皮炎（AD）是一种慢性复发性皮肤炎， 炎症性疾病，可能会影响多达10%的 人口 这种情况是特应性三联征的一部分， 包括哮喘和过敏性鼻炎。 这些疾病有很强的 遗传模式，但遗传学尚不清楚。 AD的特征是多种免疫学和 药理学异常和移植证据 研究表明，基本的异常表现在骨骼中， 骨髓细胞 缺陷如嗜碱性粒细胞组胺增加 B淋巴细胞释放和高自发性IgE产生 意味着有缺陷细胞调节。 循环的缩写 核苷酸代谢已在AD中得到证实， cAMP-磷酸二酯酶（PDE）活性升高， 低的细胞内cAMP水平可能具有净容许效应 对免疫和炎症反应的影响 色谱聚焦 对异常PDE的研究表明， 单核细胞中PDE活性的异常胞质组分， 淋巴细胞 单克隆抗体的研究进展 现在为我们提供了表征和 分离异常酶形式。 我们将扩大初步的 磷酸化作为PDE激活机制的证据 并研究蛋白水解对酶结构和活性的影响。 我们将使用免疫检测试验进行预测性筛选， 特应性个体和鉴定特定的白细胞亚群。 另一个主要的努力将针对诱导白细胞 活化标志物和异常PDE单核白细胞 AD白细胞培养物产生的免疫效应因子， 可能是通过特定的细胞因子。 最后，我们打算对脐带血白细胞进行阐述 激活因子和异常PDE活性作为预测因子 特应性和支气管肺发育不良 这些研究旨在确定导致 提供疾病的生化标志物， 异常生化和免疫机制相关 在特应性皮炎中PDE增加。

Atopic dermatitis (AD) is a chronically recurrent cutaneous inflammatory disease which may affect up to 10% of the population. The condition is part of the atopic triad which also includes asthma and allergic rhinitis. These diseases have strong hereditary patterns but the genetics is unclear. AD is characterized by a variety of immunologic and pharmacologic abnormalities, and evidence from transplant studies indicates that the basic abnormality is expressed in bone marrow cells. Defects such as increased basophil histamine release and high spontaneous IgE production by B lymphocytes imply defective cellular regulation. Abnormalities of cyclic nucleotide metabolism have been demonstrated in AD and elevated cAMP-phosphodiesterase (PDE) activity with resultant low intracellular cAMP levels may have a net permissive effect on immune and inflammatory responses. Chromatofocusing studies of abnormal PDE have demonstrated two distinctly abnormal cytosolic fractions of PDE activity in monocytes and lymphocytes. The recent development of monoclonal antibodies to PDE's now provides us with the means to characterize and isolate abnormal enzyme forms. We will expand upon preliminary evidence for phosphorylation as a mechanism of PDE activation and study proteolytic effects on enzyme structure and activity. We will use immunodetection assays for predictive screening of atopic individuals and for identifying specific leukocyte subsets. Another major effort will be directed at induction of leukocyte activation markers and abnormal PDE mononuclear leukocytes by immune effector factors produced by AD leukocyte cultures and potentially by specific cytokines. Finally we intend to study cord blood leukocytes for elaboration of activation factors and for abnormal PDE activity as predictors of atopy and bronchopulmonary dysplasia. These studies are directed at determining primary events leading to atopy, to provide biochemical markers of disease and to clarify abnormal biochemical and immunological mechanisms associated with increased PDE in atopic dermatitis.