IGG1 AND IGE RECEPTOR MECHANISMS IN LUNG

豚鼠是人类即刻超敏反应的极佳模型 肺部的反应。其中一个缺点就是免疫球蛋白IgG1抗体 本种是显性过敏性抗体。因为我们一直在 能够在豚鼠体内产生IgE，我们一直在研究 这种抗体的生物学活性。我们工作的长远目标是 了解这些抗体的区别和联系 与豚鼠的即刻超敏反应有关。 这项建议的具体目标是基于我们的调查结果 证明豚鼠IgE和IgG1抗体都将介导 抗原诱导的肺平滑肌收缩。然而，我们有 有证据表明，它们是通过不同的受体做到这一点的。因此，我们要求 问题是，如果是这样的话，与这种收缩有关的事件 回应(即调解人释放)也不同。我们将着手解决这一问题 以几种不同的方式解决问题。首先，我们将提纯IgE抗体 这在过去是很难做到的。有了这种抗体，我们可以 进行交叉抗体竞争实验(与IgG1)以加强 我们最初的发现。其次，随着输液技术的使用， 我们将不仅能够测量收缩，而且还能够测量介体释放 同时。在这些实验中，我们将有能力 操纵组织受体(用药物剂和抗体) 这使得我们能够研究收缩和收缩之间的关系 用IgE和IgG1抗体释放介质。最后，我们将隔离 取自豚鼠肺的肺肥大细胞。这个单元格已经显示出可以发挥作用 在即刻过敏反应中起核心作用。如果这是真的， 然后探讨了IgG1和IgE1的联系和区别 因为它与肺肥大细胞上的反应性有关，应该为我们提供一个 我们的组织数据的重要扩展。 肺部变态反应性疾病是一种常见于多种疾病的疾病。 个人。而从动物模型到人类的飞跃通常不是 直接，我们可以在豚鼠肺中获得重要信息 可以帮助我们理解人类肺部的类似事件。

The guinea pig is an excellent model for human immediate hypersensitivity reactions in the lung. The one drawback has been that IgG1 antibody in this species is the dominant anaphylactic antibody. Since we have been capable of producing IgE in the guinea pig, we have been studying the biologic activity of this antibody. The long range goal of our work is to understand the differences and relationships of these antibodies as they relate to immediate hypersensitivity reactions in the guinea pig. The specific aims of this proposal are based upon our findings demonstrating that both guinea pig IgE and IgG1 antibody will mediate antigen induced pulmonary smooth muscle contraction. However, we have evidence they do so through distinct receptors. Therefore, we ask the question, if this is so, are the events associated with this contractile response (i.e. mediator release) distinct also. We will approach this problem in several different ways. Firstly, we will purify IgE antibody which has been difficult to do in the past. With this antibody, we can perform crossed antibody competition experiments (with IgG1) to strengthen our original findings. Secondly, with the use of superfusion techniques, we will be able to measure not only contraction, but also mediator release simultaneously. In these experiments, we will have the capability of manipulating tissue receptors (with pharmacologic agents and antibody) which allows us to examine the relationship between contraction and mediator release with IgE and IgG1 antibodies. Lastly, we will isolate the pulmonary mast cell from guinea pig lung. This cell has been shown to play a central role in immediate hypersensitivity reactions. If this is true, then an investigation of the relationship and difference of IgG1 and IgE1 as it relates to reactivity on the pulmonary mast cell, should offer us an important extension of our tissue data. Allergic disorders of the lung are important diseases occurring in many individuals. While the leap from animal model to humans is most often not direct, we can obtain important information in the guinea pig lung that could aid in our understanding of similar events in human lung.