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.
