IGG1 AND IGE RECEPTOR MECHANISMS IN LUNG

豚鼠是人类速发型超敏反应的极好模型 肺部的反应。 一个缺点是IgG1抗体在 该物种是主要的过敏性抗体。 既然我们 能够在豚鼠中产生IgE，我们一直在研究 这种抗体的生物活性。 我们工作的长远目标是 了解这些抗体的差异和关系，因为它们 与豚鼠的速发型超敏反应有关。 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。 但我们 这表明它们是通过不同的受体来实现的。 因此，我们要求 问题是，如果是这样的话，与这种收缩相关的事件是否 反应（即介质释放）也不同。 我们会处理这个问题 问题在几个不同的方式。 首先，我们将纯化IgE抗体 这在过去很难做到。 有了这种抗体， 进行交叉抗体竞争实验（与IgG1）以加强 我们最初的发现 其次，通过使用灌注技术， 我们不仅可以测量收缩，还可以测量介质的释放， 同步 在这些实验中，我们将有能力 操纵组织受体（用药物和抗体） 这使我们能够检查收缩和收缩之间的关系， 介体释放与IgE和IgG1抗体。 最后，我们将隔离 豚鼠肺肥大细胞。 这个细胞已经被证明 在速发型超敏反应中起核心作用。 如果这是真的， 探讨IgG 1和IgE 1的关系和差异， 因为它与肺肥大细胞的反应性有关， 我们组织数据的重要扩展。 肺的过敏性疾病是发生在许多人中的重要疾病。 个体 虽然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.