PHOSPHODIESTERASE STUDIES IN ATOPIC DERMATITIS

特应性皮炎是一种炎症性皮肤病，其包括沿着 患有哮喘和过敏性鼻炎，这三种疾病被称为 特应性疾病 这些条件是遗传性的，是常见的原因， 社会和职业病。 疾病机制尚不确定， 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，因此不精确。 特应性皮炎有 最明显的免疫学和药理学异常， 研究这些异常现象以寻找基本致病因素的线索。 我们 长期目标是阐明基本的病理机制， 以确定疾病的离散实验室指标。 我们的研究比较了特应性和正常的血液白细胞。 后者 在暴露于介质后显示与atopioc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 我们观察到异常高的环AMP-磷酸二酯酶（PDE）， 特应性皮炎和其他特应性疾病患者的白细胞。 这个项目的重点是生化表征的异常 特应性白细胞的PDE和正常白细胞PDE的比较研究 淋巴细胞和单核细胞刺激组胺和其他介质。 这一模式应提供一种手段，用以评估 磷酸化和其他可能导致PDE酶异常的机制 forms. 抑制剂的研究可能会提供新的药理学见解 治疗特应性皮炎的方法。 最近的调查 利用色谱聚焦作为生化鉴定的新手段 并显示出两个不同的异常分数的PDE活性的特应性 白细胞 这些研究的未来扩展应允许澄清 这些酶的确切细胞来源，以及它们是否是 与组胺刺激的细胞中的那些相同。 合作研究 Basenji-Greyhound哮喘犬模型的白细胞循环 核苷酸异常和PDE升高，与特应性人类相似。 异常PDE的生化鉴定沿着新开发的 针对各种PDE形式的特异性抗体可以提供精确的检测方法， 特应性鼻炎的诊断和预测流行病学及遗传学研究 皮炎和其他特应性疾病。 环GMP合成和 将评估这些细胞中的代谢，以评估 不平衡环核苷酸调节作为功能性 特应性缺陷

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.