We describe experiments to investigate the functions of the eosinophil leukocyte. Present information suggests that eosinophils mediate immunity to parasites by attacking and killing susceptible forms of the parasite. One of the mechanisms by which eosinophils kill is the secretion of the eosinophil granule major basic protein (MBP) onto the surface of the parasite. Our previous results point to a role for the eosinophil and the MBP in tissue damage. In this proposal we plan to investigate further the ability of the various forms of MBP to damage cells and tissues, including mast cells, bronchial epithelium and skin. MBP will be tested alone and with eosinophil peroxidase, halide and hydrogen peroxide. Inhibitors of MBP cytotoxicity will be sought. The possibility that the eosinophil damage tissues through an innocent bystander mechanism will be tested. We will attempt to establish an animal model showing the pathologic features of bronchial asthma. The hypothesis that eosinophils damage helminthic parasites will be tested by determining whether MBP is localized to the parasite. Monoclonal antibodies to eosinophils will be produced and their ability to ablate eosinophils will be tested. Finally the monoclonal antibodies will be used to determine the role of the eosinophil in fertility.
