PHOSPHODIESTERASE STUDIES IN ATOPIC DERMATITIS

特应性皮炎是一种炎症性皮肤病，包括 哮喘和过敏性鼻炎，这三种情况称为 特应性疾病。这些情况是遗传性的，是导致 社会和职业发病率。疾病机制尚不确定，而且 没有令人满意的预防或治疗方法。诊断是 由于缺乏明确的实验室测试而不精确。特应性皮炎有 最明显的免疫学和药理学异常，我们有 研究这些异常以寻找基本致病因素的线索。我们的 长期目标是描绘基本的病理机制和 以确定该疾病的一个独立的实验室指标。 我们的研究比较了特应性和正常血白细胞。后者 在接触介体后表现出与阿托品细胞的生化相似性 如组胺、前列腺素E1和异丙肾上腺素。这种模式导致了 大鼠异常高环磷酸腺苷二酯酶(PDE)的观察 特应性皮炎和其他特应性疾病患者的白细胞。 本项目主要研究异常细胞的生化特征。 特应性白细胞中的PDE及正常人PDE的比较研究 用组胺和其他介质刺激淋巴细胞和单核细胞。 这一模型应该提供一种方法来评估 磷酸化和其他可能导致PDE酶异常的机制 表格。对抑制剂的研究可能为新的药理提供洞察力 特应性皮炎的治疗方法。最近的调查显示 利用色谱聚焦作为一种新的生化鉴定手段 并在特应性疾病中显示出两种明显的PDE活性异常 白细胞。这些研究的未来扩展应该允许澄清 这些酶的确切细胞来源以及它们是否是 与组胺刺激细胞中的相同。合作研究 巴森吉-灰狗哮喘模型显示出白细胞周期 类似于特应性人类的核苷酸异常和PDE升高。 PDE异常的生化鉴定及新进展 针对各种PDE形式的特异性抗体可以提供一种精确的 特应性疾病的诊断性、预测性流行病学和遗传学研究 皮炎等特应性疾病。环状GMP合成和 将对这些细胞的新陈代谢进行评估，以评估 不平衡的环核苷酸调节作为功能性疾病的替代原因 过敏症的缺陷。

Atopic dermatitis is an inflammatory skin disease that comprises, along with asthma and allergic rhinitis, the triad of conditions known as the atopic diseases. These conditions are hereditary and are common causes of social and occupational morbidity. Disease mechanisms are uncertain and there are no satisfactory means of prevention or cure. Diagnosis is imprecise due to lack of distinct laboratory tests. Atopic dermatitis has the most pronounced immunologic and pharmacologic aberrancies and we have studied these abnormalities for clues as to basic causative factors. Our long-term objectives are to delineate the basic pathologic mechanisms and to identify a discrete laboratory indicator of the disease. Our studies have compared atopic and normal blood leukocytes. The latter show biochemical similarities to atopioc cells after exposure to mediators such as histamine, prostaglandin E1 and isoproterenol. This model led to our observation of abnormally high cyclic AMP-phosphodiesterase (PDE) in leukocytes of patients with atopic dermatitis and other atopic conditions. This project is focused upon biochemical characterization of the abnormal PDE in atopic leukocytes and on comparative studies of the PDE in normal lymphocytes and monocytes stimulated with histamine and other mediators. This model should provide a means for evaluating the role of phosphorylation and other mechanisms which may lead to abnormal PDE enzyme forms. Studies with inhibitors may provide insight into new pharmacologic modalities for treating atopic dermatitis. Recent investigations have utilized chromatofocusing as a novel means of biochemical identification and have shown two distinct abnormal fractions of PDE activity in atopic leukocytes. Future extensions of these studies should allow clarification of the exact cell source of these enzyme forms and whether they are identical with those in histamine stimulated cells. Collaborative studies of the Basenji-Greyhound dog model of asthma have shown leukocyte cyclic nucleotide abnormalities and elevated PDE similar to atopic humans. Biochemical identification of abnormal PDE along with newly developed specific antibodies to various PDE forms may provide a means of precise diagnostic, and predictive epidemiologic and genetic studies of atopic dermatitis and the other atopic diseases. Cyclic GMP synthesis and metabolism in these cells will be assessed to evaluate the possibility of imbalanced cyclic nucleotide regulation as an alternate cause of functional defects in atopy.