PHOSPHODIESTERASE STUDIES IN ATOPIC DERMATITIS

特应性皮炎(AD)是一种慢性复发性皮肤 炎症性疾病，可能影响高达10%的 人口。这种情况是特应性三联症的一部分，也是 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的特点是具有多种免疫学和 药理上的异常和移植的证据 研究表明，基本的异常表现在骨骼中 骨髓细胞。嗜碱性粒细胞组胺增加等缺陷 B淋巴细胞释放和高自发产生免疫球蛋白E 意味着细胞调节有缺陷。循环异常 核苷酸代谢在阿尔茨海默病和 CAMP-磷酸二酯酶(PDE)活性升高 低的细胞内cAMP水平可能具有净允许效应 免疫和炎症反应。色散聚焦 对异常PDE的研究清楚地证明了两个 单核细胞胞浆中PDE活性的异常部分 淋巴细胞。单抗的研究进展 TO PDE‘s现在为我们提供了表征和 分离出异常的酶形式。我们将在初步的基础上进行扩展 磷酸化是PDE激活机制的证据 研究蛋白水解酶对酶结构和活性的影响。 我们将使用免疫检测方法进行预测性筛查 特应性个体，并用于识别特定的白细胞亚群。 另一个主要的努力将是诱导白细胞 活化标志物与异常PDE单核白细胞 阿尔茨海默病患者白细胞培养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详细研究。 激活因子和PDE活性异常作为预测因子 特应性疾病和支气管肺发育不良。 这些研究旨在确定主要事件导致 特应性，提供疾病的生化标记物，并澄清 与生化和免疫相关的异常机制 特应性皮炎的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.