It is well established that IgG receptors are of major importance in promoting functions of mononuclear phagocytes. By contrast little is known concerning receptors for IgE and IgA on these cells. Detailed studies on the expression and regulation of these receptors have been limited by their low affinity, and by difficulty in obtaining sufficient numbers of cells bearing these receptors. Lack of human IgE and IgA antibodies to suitable targets has prevented examination of the role of these Ig's in phagocyte function. The importance of expression of Fc receptors for IgE and IgA to function of mononuclear phagocytes will be explored in this proposal using both human monocytes and a model system employing myeloid cell lines. The U-937 monocyte-like line expresses high levels of IgE receptors after gamma interferon stimulation, and 1,25-dihydroxyvitamin D3 treated HL-60 cells express IgA receptors. Since it is now evident that Ig polymers bind more avidly to Fc receptors than do monomers, the binding characteristics of IgE and IgA to their respective receptors will be examined using monomers and defined polymers of human myeloma IgE and IgA. The modulation of these receptors following binding of monomer or polymer IgE, IgA or IgG to the surface monocytes, U-937 and HL-60 cells will be investigated. Cells will also be treated with factors such as lymphokines, interferons and vitamins to study the influence of these compounds on receptor expression. Monocytes will be studied for Fc receptor expression and modulation directly after isolation and at various times during in vivo maturation into macrophages. Covalent linking of human IgE and IgA to Fab regions specific for target cells will permit studies on receptor-mediated function. Cells expressing various levels of Fc receptors after the procedures outlined above will be tested for ability to perform IgE, IgA and IgG mediated phagocytosis, ADCC, and lysosmal enzyme and leukotriene secretion.
