PATHOGENESIS OF ALLERGIC DISEASES OF THE SKIN & LUNGS

皮肤过敏性疾病的发病机制

• 批准号: 3105020
• 负责人: ALLEN P KAPLAN
• 金额: $ 35.45万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3105020
• 关键词: Lyme disease; asthma; hereditary angioneurotic edema; inflammation; urticaria; vasculitis

The Allergic Diseases Center at SUNY-Stony Brook studies pathogenic mechanisms of tissue injury in a wide variety of diseases to include physically induced hives, chronic urticaria and angioedema, hereditary angioedema, Lyme disease, cryoglobulinemia (and other vasculitides) and asthma. We will study molecular mechanisms of histamine release from basophils and mast cells, activation of the classical complement pathway, and activation of the coagulation- kinin pathway, as applied to these diseases. We will develop new methods for assessment of kinin formation in human disease focusing upon cleavage of kininogen and determination of bradykinin and its degradation products. We will purify and characterize Histamine Releasing Factors(s) (HRF) which are cytokines released from lymphocytes and/or monocytes to cause basophils and mast cell degranulation and determine its relationship to histamine-releasing cytokines we have identified such as interleukin 3 and GM-CSF. We will study possible mechanisms by which a temperature change initiates histamine release in cold urticaria and the role of temperature (thermal amplitude) of cryoproteins to cause cryoprecipitation and complement activation in cryoglobulinemia. The role of neuropeptides as mediators of hives will be assessed, particularly as they pertain to cholinergic urticaria, and we will continue studies of the time course of mediator release and histologic assessment of chronic idiopathic urticaria and angioedema. The non-necrotizing perivascular inflammation of chronic urticaria will be compared to the vasculitis of cryoglobulinemia, late phase reactions, and contact dermatitis. Our assessment of hereditary angioedema will include new methods for diagnosis of the various types, assessment of Cl NIH synthesis in vitro, and identification of the vasoactive substance which causes the swelling. Lyme disease is endemic on Long Island and spreading throughout the Northeast. We propose to develop new, more accurate and specific methods of diagnosis, study immune responsiveness to B. burgdorfei, and assess its ability to activate mediator systems during infection and during Herxheimer reactions associated with therapy. Finally, we will study the interrelationship of distribution of inhaled particles in asthma with mechanical parameters such as the formation of flow-limiting segments, obstructive ventilatory parameters, and mucociliary clearance.

SUNY-Stony Brook的过敏性疾病中心研究致病性 多种疾病的组织损伤机制 包括物理诱导的蜂箱，慢性荨麻疹和血管性水肿， 遗传性血管性水肿，莱姆病，冷冻球蛋白血症（以及其他 Vasculitides）和哮喘。 我们将研究分子机制 组胺从嗜碱性粒细胞和肥大细胞释放，激活 经典补体途径和凝结的激活 Kinin途径，适用于这些疾病。 我们将开发新的 评估人类疾病聚焦中基因蛋白形成的方法 裂解动力学并确定巴拉迪金蛋白及其 降解产品。 我们将纯化并表征组胺 释放因子（HRF）是从 淋巴细胞和/或单核细胞引起嗜碱性粒细胞和肥大细胞 脱粒并确定其与组胺释放的关系 我们已经确定的细胞因子，例如白介素3和GM-CSF。 我们 将研究温度变化的可能机制 在冷荨麻疹中启动组胺释放和 冷冻蛋白的温度（热振幅）引起 冷冻药物和补体激活中的冷冻球蛋白血症。 将评估神经肽作为蜂巢介质的作用， 特别是当它们与胆碱能荨麻疹有关时，我们将 继续研究调解员释放的时间过程和 慢性特发性荨麻疹的组织学评估和 血管性水肿。 非全肿的周围血管周期炎症 将慢性荨麻疹与血管炎进行比较 冷冻球蛋白血症，晚期反应和接触性皮炎。 我们对遗传性血管性水肿的评估将包括新方法 为了诊断各种类型，评估Cl NIH合成 体外，并鉴定血管活性物质 导致肿胀。 莱姆病在长岛和 遍布东北。 我们建议开发新的 更准确，更具体的诊断方法，研究免疫 对B. burgdorfei的响应能力，并评估其激活的能力 感染期间和Herxheimer反应期间的介体系统 与治疗相关。 最后，我们将研究 哮喘吸入颗粒分布的相互关系 与机械参数（例如流量限制的形成） 段，阻塞性通气参数和粘毛参数 清除。