Human peripheral blood neutrophils have Fc receptors for serum IgA immunoglobulins, but these receptors require activation before they are functional. Recent studies from our laboratory show that granulocyte- macrophage colony-stimulating factor (GM-CSF) enhances neutrophil IgA- mediated phagocytosis. The goal of this research proposal is to characterize the molecular events leading to activation of neutrophil IgA Fc receptors by GM-CSF. Our studies will encompass the biochemistry and physiology of neutrophil IgA Fc receptor activation, including studies to molecularly characterize neutrophil IgA Fc receptors. These goals will be achieved by the following specific aims to: 1. Produce monoclonal antibodies (MAbs) to neutrophil IgA Fc receptors. The MAbs will be used to study the biosynthesis of the receptor, characterize the binding site for IgA, and assess receptor internalization, degradation, or recycling. 2. Characterize the biological functions of neutrophil IgA Fc receptors activated by GM-CSF. Studies will be done to establish new models of IgA- mediated phagocytosis and ADCC in response to GM-CSF using micobial organisms and tumor cells. 3. Characterize the biochemical events in neutrophil IgA Fc receptor activation by GM-CSF. We will examine the role of protein synthesis, GTP binding proteins, changes in calcium fluxes, receptor phosphorylation, glycosylation, and receptor structure in response to GM-CSF. We will determine if IgA receptors are internalized and degraded, or recycled. 4. Clone the gene(s) encoding neutrophil IgA Fc receptors.
