Airways eosinophils as antigen-presenting cells-asthma

气道嗜酸性粒细胞作为抗原呈递细胞-哮喘

• 批准号: 6895229
• 负责人: PETER F WELLER
• 金额: $ 38.25万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895229
• 关键词: Aspergillus; CD antigens; airborne allergen; antibody receptor; antigen presenting cell; asthma; cell migration; cellular immunity; clinical research; eosinophil; genetically modified animals; helper T lymphocyte; human tissue; immunoglobulin E; integrins; laboratory mouse; receptor expression; tissue /cell culture

Description (provided by applicant): Studies will investigate the ability of eosinophils to serve as antigen-presenting cells that contribute to propagating lymphocyte-dependent, IgE-mediated response to inhaled antigens in the respiratory tract. Eosinophils are prominent cellular components of allergic airway responses. While many cells function as antigen-presenting cells, eosinophils have distinct capabilities within the airway. First, eosinophils are present in the airway lumina of asthmatics; and these eosinophils in vivo express requisite class II MHC proteins and critical lymphocyte costimulatory proteins. Second, eosinophils contain preformed stores of cytokines that may be rapidly mobilized for extra cellular release to modulate lymphocyte-dependent responses. Third, unlike B cells and dendritic cells that are capable of presenting soluble protein antigens, eosinophils, like macrophages, are especially able to degrade particulate antigens. Alveolar macrophages are poor antigen-presenting cells. In contrast, eosinophils could present peptides derived from particulate inhaled allergens. Fourth, antibodies of several classes, by Fc receptor-mediated mechanisms, can dramatically enhance antigen uptake and presentation by antigen-presenting cells. Eosinophils with their IgE, IgA, and IgG antibodies receptors are well suited to internalize and present allergens recognized by allergen-specific IgE, IgA, and IgG antibodies present in the respiratory tract. Fifth, eosinophil trafficking from the airway lumen into lymphocytes provides a mechanism for antigens inhaled into the airways to be processed and transported into tissues for presentation to lymphocytes. Hypotheses are that eosinophils are effective at presenting inhaled antigens to lymphocytes, that this eosinophil antigen processing and trafficking occur in vivo within the airways, that eosinophil high affinity IgE receptors function to enhance eosinophil antigen presentation of allergens, and that antigen presentation by eosinophils, perhaps based on their release of preformed, cytokines, skews Th2-mediated responses to inhaled antigens. Studies aim to define the capacity of human eosinophils in vitro to function as antigen-presenting cells and to define the role of eosinophil IgE receptors in facilitating antigen presentation by eosinophils. These studies of eosinophils active in asthma focus on the roles of eosinophils in propagating the chronic airway inflammation of asthma. Roles for eosinophils as antigen-presenting cells in sustaining allergic responses to inhaled particulate allergens would provide insights into the characteristically chronic nature of allergic diseases.

描述（由申请人提供）：研究将调查以下人员的能力： 嗜酸性粒细胞作为抗原呈递细胞，有助于 传播淋巴细胞依赖性、IgE 介导的对吸入抗原的反应 呼吸道。嗜酸性粒细胞是重要的细胞成分 过敏性气道反应。虽然许多细胞发挥抗原呈递作用 嗜酸性粒细胞在气道内具有独特的功能。第一的， 哮喘患者气道腔内存在嗜酸性粒细胞；还有这些 嗜酸性粒细胞在体内表达必需的 II 类 MHC 蛋白和关键的 淋巴细胞共刺激蛋白。其次，嗜酸性粒细胞含有预先形成的 细胞因子的储存可被快速动员以释放细胞外 调节淋巴细胞依赖性反应。第三，与B细胞不同的是 能够呈递可溶性蛋白抗原的树突状细胞， 嗜酸性粒细胞，如巨噬细胞，特别能够降解颗粒物 抗原。肺泡巨噬细胞是较差的抗原呈递细胞。在 相比之下，嗜酸性粒细胞可以呈递源自吸入颗粒物的肽 过敏原。第四，由Fc受体介导的几类抗体 机制，可以显着增强抗原的摄取和呈递 抗原呈递细胞。嗜酸性粒细胞及其 IgE、IgA 和 IgG 抗体 受体非常适合内化并呈现被识别的过敏原 呼吸道中存在过敏原特异性 IgE、IgA 和 IgG 抗体 道。第五，嗜酸性粒细胞从气道腔转运至淋巴细胞 提供了一种将抗原吸入气道进行处理的机制 转运到组织中呈递给淋巴细胞。假设是 嗜酸性粒细胞能够有效地将吸入的抗原呈递给淋巴细胞， 这种嗜酸性粒细胞抗原的加工和运输发生在体内 气道中，嗜酸性粒细胞高亲和力 IgE 受体的功能增强 过敏原的嗜酸性粒细胞抗原呈递，以及抗原呈递 嗜酸性粒细胞，可能基于它们释放的预形成细胞因子、偏斜 Th2 介导的对吸入抗原的反应。研究旨在定义 人嗜酸性粒细胞在体外充当抗原呈递细胞的能力 并确定嗜酸性粒细胞 IgE 受体在促进抗原形成中的作用 由嗜酸性粒细胞呈递。这些关于哮喘中活跃的嗜酸性粒细胞的研究 关注嗜酸性粒细胞在慢性气道传播中的作用 哮喘的炎症。嗜酸性粒细胞作为抗原呈递细胞的作用 维持对吸入颗粒过敏原的过敏反应将提供 深入了解过敏性疾病的慢性特征。