These investigations are designed to examine and define the mechanisms by which human phagocytic cells, in particular neutrophils, kill pathogenic microorganisms and to attempt correction of these mechanisms when defects are found. A broad based approach will be employed which will involve: 1) screening of patients with recurrent infections for phagocytic cell defects; 2) exploration of the role of various oxidative events in the function of phagocytic cells, concentrating on the role of surface mechanisms in triggering the leukocyte respiratory burst, the role of myeloperoxidase in the metabolic and microbicidal events of the PMN, and the operation of other oxidative intermediates in antimicrobial activity; 3) Using monoclonal antibodies which have been developed to the PMN and macrophage cell membrane, functional mapping of the membrane antigens will be carried out and further monoclonal antibodies developed as necessary. These same monoclonal antibodies will be used as carriers of specific enzymes, such as myeloperoxidase or oxidases into cell in which they may be missing to determine if defective mechanisms can be corrected or if they can be used as cytocidal reagents.
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