SCOR--OCCUPATIONAL AND IMMUNOLOGICAL LUNG DISEASES

SCOR--职业性和免疫性肺病

• 批准号: 2223061
• 负责人: DAVID M. CENTER
• 金额: $ 81.94万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2223061
• 关键词: immunopathology; lung disorder; occupational disease /disorder

The thematic hypotheses of this SCOR are that CD4+ leukocytes have central roles in the inflammation associated with granuloma formation, and that cell surface CD4 is not only a marker of differentiation but plays an important receptor function in initiating immune, inflammatory and microbicidal activity. This SCOR represents the collaborative efforts of a group of scientists who have shared common interests for almost ten years. In four interrelated projects, we propose to study selected functions of the three major CD4+ cell types associated with granuloma formation, CD4+ T lymphocytes, CD4+ monocytes/macrophages and CD4+ eosinophils. Peripheral blood, bronchoalveolar lavage and tissue cells will be used in studies designed to determine the function of CD4 on normal leukocytes; on leukocytes from individuals with normal host defenses, but with infectious granulomatous diseases (i.e. M. tuberculosis); on leukocytes from individuals with non-infectious granulomatous lung disease (i.e. Sarcoidosis); and on leukocytes from individuals with immunodeficiency states known to affect CD4+ cells (i.e. HIV-1 infected individuals with and without opportunistic infections). Several discoveries by members of the SCOR make the proposed studies unique. Dr. Center's laboratory has cloned and Lymphocyte Chemoattractant Factor (LCF) which is a natural lymphokine ligand for CD4. This ligand makes it possible to identify the signal transduction pathways used by CD4, alternative functions for CD4 on the T cell, and to identify primary functions for CD4 on the monocyte, alveolar macrophage and eosinophil. Projects 1 (Dr. Center), 3 (Dr. Bernardo) and 4 (Dr. Berman) develop extensive preliminary data that LCF interacts with CD4 causing PI turnover into IP3, Ca++ mobilization, migratory responses and up regulation of IL2r and MHC II antigens on both T cells and monocytes; and Project 2 (Dr. Weller) has recently identified CD4 on the surface of eosinophils demonstrating it to be a functional chemotactic receptor for LCF. The SCOR is designed in a completely integrated fashion in which each of the four projects depends heavily upon the reagents, resources, and special methods of the others in order to study the function of CD4 on CD4+ cells and their participation in granulomatous lung diseases.

该SCOR的主题假设是CD4+白细胞具有中央 与肉芽肿形成相关的炎症中的作用， 细胞表面CD4不仅是分化的标记，而且扮演 重要的受体功能在发起免疫，炎症和 微生物活性。 此SCOR代表了 一群分享了近十个共同利益的科学家 年。 在四个相互关联的项目中，我们建议研究选定的 与肉芽肿相关的三种主要CD4+细胞类型的功能 形成，CD4+ T淋巴细胞，CD4+单核细胞/巨噬细胞和CD4+ 嗜酸性粒细胞。 外周血，支气管肺泡灌洗和组织细胞 将用于旨在确定CD4在正常的研究中 白细胞；关于有正常宿主防御措施的人的白细胞，但 感染性肉芽肿性疾病（即结核病）；在 来自非感染性肉芽肿性肺部病人的白细胞 （即结节病）；以及来自患有患者的白细胞 已知会影响CD4+细胞的免疫缺陷状态（即HIV-1感染 患有和没有机会感染的人）。 SCOR成员的几个发现进行了拟议的研究 独特的。 中心博士的实验室已克隆和淋巴细胞化学吸引力 因子（LCF），它是CD4的天然淋巴细胞配体。 这个配体 可以识别CD4使用的信号转导途径 T细胞上CD4的替代功能，并识别主要功能 CD4在单核细胞，肺泡巨噬细胞和嗜酸性粒细胞上的功能。 项目1（中心博士），3（Bernardo博士）和4（Berman博士）发展 LCF与CD4相互作用的广泛初步数据导致PI营业额 进入IP3，CA ++动员，迁移反应和IL2R的调节 T细胞和单核细胞上的MHC II抗原；和项目2（博士 Weller）最近在嗜酸性粒细胞表面鉴定了CD4 证明它是LCF的功能性趋化受体。 SCOR以完全整合的方式设计 这四个项目在很大程度上取决于试剂，资源和特别 其他方法是为了研究CD4在CD4+细胞上的功能 以及他们参与肉芽肿性肺部疾病。