This application proposes to examine the role of the eosinophil in human disease. Prior studies have shown that eosinophil granule proteins have the ability to damage tissues and that the degree of participation of the eosinophil in a given inflammatory reaction cannot be determined simply by counting the numbers of eosinophils in tissues. However, these prior studies have examined only one granule protein, the major basic protein, as an indicator of the eosinophil's contribution to pathologic processes. Therefore, in the proposed studies we wish to establish assays for all of the major eosinophil granule proteins and to use these measurements as indicators of degranulation in studies of disease. First, we describe the development and standardization of new radioimmunoassays and immunofluorescence assays for eosinophil granule proteins, including the eosinophil-derived neurotoxin, the eosinophil cationic protein and the eosinophil peroxidase. These assays will be used to assess eosinophil degranulation in body fluids and tissues along with already described assay for the eosinophil granule major basic protein. Second, assays for eosinophil granule proteins will be used to investigate diseases such as the toxic oil syndrome, systemic fibrosing syndromes, tropical diseases, gastrointestinal diseases, vasculitic diseases, and colon cancer. Based on preliminary studies, we believe that eosinophil degranulation occurs in all of these diseases. Third, eosinophil degranulation will be studied in vitro to determine whether degranulating eosinophils die, to investigate eosinophil activating substances, and to establish model systems for analyses of the role of IgG and IgE antibodies in degranulation. Fourth, light density eosinophils will be analyzed to determine the morphologic basis for their reduced density and to determine whether they degranulate more readily than normodense eosinophils. Fifth, we describe experiments to test the ability of eosinophil granules to stimulate fibroplasia; prior studies have shown a striking association between degranulation and fibrous tissue deposition. Finally, we describe protocol for investigation of patients with marked blood eosinophilia.
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