CELLULAR BASIS OF HYPERSENSITIVITY DISEASES IN HUMANS

该计划由两个面向疾病的子部分组成，肺和 皮肤病学，通过相互关注两种细胞 类型，肥大细胞和嗜酸性粒细胞，它们的产物和疾病， 可能是由于其组织表型的失调， 直接或通过其他细胞类型介导的炎性潜能。 一 一个特别的项目是将目前对病理生物学的理解 支气管哮喘及其治疗的城市少数民族人口， 一个示范和教育项目，并进行效益评估。 文化上适当的教育方案将针对这两个 哮喘患者和他们的私人医生增加他们的 了解这种疾病的病理生物学以及 通过使用家庭峰值流量客观监测肺功能 测量和基于健康中心的肺量计。 肺 在这一小节中，LTE 4的尿排泄将被用作 正常人内源性半胱氨酰白三烯的产生 诱导气道高反应性和支气管哮喘患者 作为疾病活动或不同病理生物学的可能指标 分组。 组织和循环细胞因子的存在能够 改变嗜酸性粒细胞的表型，以增加生存力， 不仅在慢性嗜酸性粒细胞白血病中寻求配体介导的反应， 肺炎，但也在大疱性类天疱疮。 表达调控 变应性支气管肺炎单核/巨噬细胞β-葡聚糖受体 将相对于未感染的患者评估曲霉病， 皮质类固醇治疗的效果。 识别性抗肽 针对一组人肥大细胞的抗体和分子探针 蛋白酶将被制备并用于分析肥大细胞的成熟， 体外，利用从平行研究中获得的见解和系统， 小鼠肥大细胞系统。 特别值得注意的是，这些探测器将 用于对正常人、正常人和病变人肥大细胞进行表型分析 身体过敏患者的部位（运动相关的过敏反应， 冷诱导荨麻疹、皮肤划痕症和胆碱能性荨麻疹），全身性 肥大细胞增多症和大疱性类天疱疮。 由于歧视的数量 探针的增加，预计肥大细胞的表型， 沿着颗粒结构和细胞的超微结构分析 分布，可以揭示各种表型的病理生物学重要性 同时还提供了对组织部位在 表型调控。

The program is composed of two disease-oriented subsections, pulmonary and dermatologic, which are integrated through mutual focus upon two cell types, the mast cell and the eosinophil, their products and diseases which likely result from the dys-regulation of their tissue phenotype and phlogistic potential mediated directly or via additional cell types. A particular program is to transfer the current understanding of pathobiology of bronchial asthma and its treatment to urban minority populations through a demonstration and education project with assessment of benefit. Culturally appropriate educational programs will be targeted to both patients with asthma and their personal physicians to increase their understanding of the pathobiology of this disease and the importance of objective monitoring of lung function through the use of home peak flow measurements and Health Center based spirometry. In the pulmonary subsection, the urinary excretion of LTE4 will be used as an index of the endogenous production of the cysteinyl leukotrienes in normal subjects with induced airway hyper-responsiveness and in patients with bronchial asthma as a possible index of disease activity or of distinct pathobiologic subgroups. The presence of tissue and circulating cytokines capable of altering the eosinophil phenotype so as to augment viability and prime for ligand mediated responses will be sought not only in chronic eosinophilic pneumonia but also in bullous pemphigoid. The regulation of expression of beta-glucan receptors on monocyte/macrophages in allergic bronchopulmonary aspergillosis will be assessed relative to uninfected patients and the effects of treatment with corticosteroids. Discriminatory anti-peptide antibodies and molecular probes directed against a panel of human mast cell proteases will be prepared and used to analyze mast cell maturation in vitro, utilizing insights and systems gained from parallel studies in the mouse mast cell system. Of particular note is that these probes will be used to phenotype human mast cells in normals and at normal and lesional sites of patients with physical allergies (exercise-associated anaphylaxis, cold-induced urticaria, dermographism, and cholinergic urticaria), systemic mastocytosis, and bullous pemphigoid. As the number of discriminatory probes increases, it is anticipated that the phenotyping of mast cells, along with ultrastructural analysis of granule structure and cell distribution, may reveal the pathobiologic importance of various phenotypes while also providing insight into the role of the tissue site in the regulation of phenotype.