IGG1 AND IGE RECEPTOR MECHANISMS IN LUNG

豚鼠是研究肺功能的良好模型 即刻过敏反应。在这个物种中，IgG1是 主要为过敏性抗体，但可产生IgE抗体 在某些情况下。一段时间以来，我们一直是 豚鼠IgE抗体的生物活性研究 与IgG1反应性有关，并作为人IgE抗体的模型 即刻超敏反应中的活性。因此， 我们研究的长期目标一直是，并将继续是 对IgG1和IgE区别与联系的认识 与肺即刻超敏反应相关的抗体 在豚鼠身上的反应。我们建议的具体目标是 基于我们研究中的三个根本性的重要发现。 IgG1和IgE都会引起肺平滑肌收缩， 而是通过不同的受体；不同浓度的 当这些受体被激活时，释放的介质；以及 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 围绕着另一位参与肺部事务的调解人的问题 收缩反应，以及不同种群的肥大 细胞(如果存在的话)表面有IgG1或IgE受体 这是我们组织发现的基础。基于技术 我们已经在我们的实验室里建立了，我们将接近这些 以两种方式提问。首先，我们将检测致敏抗体 肺组织利用灌流技术。在这 程序，收缩反应和介体释放 可在抗原刺激致敏组织后进行测量。在……里面 我们将专门为其他人评估这些实验 介质(由肥大细胞或其他肺细胞释放) 参与收缩反应。第二，我们将隔离 肺组织中的肺肥大细胞，检查这些细胞 调解人释放中的关系和分歧停职 IgG1、IgE抗体介导的肥大细胞检测 表面IgG1和IgE抗体受体，并检测这些细胞 对于功能和表型的异质性。过敏性疾病 肺部是许多人都会患上的重要疾病。 我们检查我们在双肺中提出的问题的能力 组织和分离的肺细胞给我们提供了一个重要的机会 探讨肺即刻发病的基本机制 超敏反应有助于我们理解 在人类肺部也发生了类似的事件。

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.