CELLULAR BASIS OF HYPERSENSITIVITY DISEASES IN HUMANS

该计划由两个以疾病为导向的小节组成，肺科和 皮肤科，通过相互聚焦于两个细胞而整合 肥大细胞和嗜酸性粒细胞的类型、其产物和疾病 可能是由于它们的组织表型和 直接或通过其他细胞类型介导的炎性潜能。一个 特别的计划是将目前对病理生物学的理解 城市少数民族人群哮喘的流行及治疗 进行效益评估的示范教育项目。 与文化相适应的教育项目将针对这两个群体 哮喘患者及其私人医生增加他们的 了解本病的病理生物学及本病的重要性 目的应用家庭峰值流量监测肺功能 基于测量和健康中心的肺活量测定法。在肺中 小节中，尿液LTE4的排泄量将被用作 正常人内源性半胱氨酸白三烯的产生 诱导的气道高反应性与哮喘患者的关系 作为疾病活动性或不同病理生物学的可能指标 子组。组织和循环细胞因子的存在能够 改变嗜酸性粒细胞表型以提高存活率 将不仅在慢性嗜酸性粒细胞增多症中寻求配体介导的反应 肺炎，但也是大疱性类天疱疮。基因表达的调控 变态反应性支气管肺单核/巨噬细胞上的β-葡聚糖受体 曲霉菌病将相对于未感染的患者进行评估， 皮质类固醇治疗的效果。区别性抗肽 针对一组人肥大细胞的抗体和分子探针 将制备蛋白酶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，这些探测器将被 用于正常人、正常人和皮损患者的肥大细胞表型 身体过敏患者的地点(运动相关过敏反应， 寒冷性荨麻疹、皮纹病和胆碱能性荨麻疹)，系统性 肥大细胞增多症和大疱性类天疱疮。因为歧视的数量 探针增加，预计肥大细胞的表型， 颗粒结构和细胞的超微结构分析 分布，可能揭示各种表型的病理生物学重要性 同时也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.