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: 6469461
• 负责人: PETER F WELLER
• 金额: $ 34.43万
• 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 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6469461
• 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)：研究将调查以下能力 嗜酸性粒细胞作为抗原提呈细胞，有助于 传播性淋巴细胞依赖的IgE介导的吸入性抗原反应 呼吸道。嗜酸性粒细胞是主要的细胞成分 过敏性呼吸道反应。虽然许多细胞的功能是作为抗原递呈 细胞，嗜酸性粒细胞在呼吸道内有不同的功能。第一, 哮喘患者的气道腔中存在嗜酸性粒细胞；而这些 体内嗜酸性粒细胞表达必需的II类MHC蛋白 淋巴细胞共刺激蛋白。第二，嗜酸性粒细胞含有预制的 储存的细胞因子可以被迅速动员起来，以供细胞外释放 来调节淋巴细胞依赖的反应。第三，不同于B细胞和 树突状细胞能够呈递可溶性蛋白抗原， 嗜酸性粒细胞，就像巨噬细胞一样，尤其能够降解颗粒。 抗原。肺泡巨噬细胞是一种较差的抗原提呈细胞。在……里面 相比之下，嗜酸性粒细胞可以提供吸入颗粒物所产生的多肽 过敏原。第四，Fc受体介导的几类抗体 机制，可以显著增强抗原的摄取和呈递，通过 抗原提呈细胞。嗜酸性粒细胞及其IgE、IgA和IgG抗体 受体非常适合内化和呈现由 呼吸道中存在的过敏原特异性IgE、IgA和Ig G抗体 一条小路。第五，嗜酸性粒细胞从气道腔进入淋巴细胞 提供一种机制，使吸入到呼吸道中的抗原被处理并 被运送到组织中，呈递给淋巴细胞。假设是 嗜酸性粒细胞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处理和贩运在体内发生在 呼吸道，嗜酸性粒细胞高亲和力IgE受体功能增强 变应原的嗜酸性粒细胞抗原递呈，以及通过 嗜酸性粒细胞，可能基于它们释放预先形成的细胞因子、偏斜 Th2介导的对吸入性抗原的反应。研究的目的是定义 体外培养的人嗜酸性粒细胞作为抗原提呈细胞的能力 并确定嗜酸性粒细胞IgE受体在易化抗原中的作用 嗜酸性粒细胞的陈述。嗜酸性粒细胞在哮喘中的活性研究 关注嗜酸性粒细胞在慢性呼吸道增殖中的作用 哮喘的炎症。嗜酸性粒细胞作为抗原提呈细胞在脑血管疾病中的作用 持续对吸入性颗粒过敏原的过敏反应将提供 对过敏性疾病特有的慢性本质的洞察。