IGG1 AND IGE RECEPTOR MECHANISMS IN LUNG

豚鼠是研究肺的极好模型 速发型超敏反应 在这个物种中，IgG 1是 主要过敏性抗体，但可产生IgE抗体 在某些情况下。 一段时间以来， 研究豚鼠IgE抗体的生物学活性， 与IgG 1反应性相关，并作为人IgE抗体的模型 在速发型超敏反应中的活性。 因此 我们研究的长期目标一直是并将继续是一个 了解IgG 1和IgE的差异和关系 与肺速发型超敏反应相关的抗体 豚鼠的反应。 我们建议的具体目标是 基于我们研究中的三个重要发现 IgG 1和IgE均引起肺平滑肌收缩， 而是通过不同的受体， 当这些受体被激活时释放的介质;以及 提示豚鼠肺肥大细胞异质性的证据。 我们根据这些发现提出的问题 围绕着另一个涉及肺的介质的问题 收缩反应，以及是否不同群体的肥大细胞 细胞（如果存在）表面有IgG 1或IgE受体 这是我们组织发现的基础 基于技术 我们已经在实验室建立了，我们将接近这些 提问有两种方式。 首先，我们将检查致敏抗体 肺组织利用灌注技术。 在这 过程中，收缩反应和介质释放 可以在致敏组织的抗原刺激后测量。 在 我们将专门评估这些实验， 介质（由肥大细胞或其他肺细胞释放） 参与了收缩反应。 第二，我们将隔离 从肺组织中提取肺肥大细胞，检查这些细胞 中介释放的关系和差异的暂停 通过IgG 1和IgE抗体介导，探测分离的肥大细胞 表面IgG 1和IgE抗体受体，并检查这些细胞 功能和表型的异质性。 过敏性疾病 肺是发生在许多个体中的重要疾病。 我们检查我们在两个肺中提出的问题的能力 组织和分离的肺细胞给了我们一个重要的机会， 探讨肺动脉高压发生的基本机制 超敏反应，可以帮助我们了解 人类肺部也有类似的情况。

The guinea pig is an excellent model for studying pulmonary immediate hypersensitivity reactions. In this species, IgG1 is the major anaphylactic antibody, but IgE antibody can be produced under certain circumstances. For some time we have been studying the biologic activity of guinea pig IgE antibody as it relates to IgG1 reactivity and as a model of human IgE antibody activity in immediate hypersensitivity reactions. Therefore, the long range goal of our research has been and continues to be an understanding of the differences and relationships of IgG1 and IgE antibodies as they relate to pulmonary immediate hypersensitivity reactions in the guinea pig. The specific aims of our proposal are based upon three fundamentally important findings in our studies. Both IgG1 and IgE cause pulmonary smooth muscle contraction, but through separate receptors; differences in concentrations of mediators released when these receptors are activated; and evidence to suggest heterogenity of guinea pig lung mast cells. The questions we have formulated based upon these findings center around the issues of another mediator involved in the lung contractile responses, and whether different populations of mast cells (if they do exist) have IgG1 or IgE receptors on their surface and this is the basis for our tissue findings. Based upon techniques we have established in our laboratory, we will approach these questions in two ways. First, we will examine antibody sensitized pulmonary tissue utilizing the superfusion technique. In this procedure, both the contractile response and mediators released can be measured after antigen stimulation of sensitized tissue. In these experiments we will specifically be evaluating for other mediators (either released by mast cells or other pulmonary cells) involved in the contractile response. Second, we will isolate pulmonary mast cells from lung tissue, examine these cell suspensions for relationships and differences in mediator release mediated by IgG1 and IgE antibody, probe the isolated mast cell surface IgG1 and IgE antibody receptors, and examine these cells for functional and phenotypic heterogenity. Allergic disorders of the lung are important diseases occurring in many individuals. Our ability to examine the questions we have asked in both lung tissue and isolated lung cells gives us an important opportunity to investigate basic mechanisms of pulmonary immediate hypersensitivity reactions that could aid in our understanding of similar events in human lung.