This subproject investigates the 40 kilodalton receptor (FcRII) for the Fc portion of immunoglobulin G that is present on the membranes of human polymorphonuclear neutrophilic leukocytes (PMN). We have previously shown that crosslinking this receptor with the monoclonal anti-receptor antibody KuFc79 activates the PMN as assessed by lysosomal enzyme release and the generation of superoxide, and that these responses are partially inhibited by pertussis toxin. We now wish to study the mechanisms that transduce the signal generated by crosslinking FcRII on the exterior of the PMN. These include calcium mobilization, phosphatidlyinositol metabolism, protein kinase C activation, guanine nucleotide binding proteins and protein phosphorylation. The consequences of crosslinking FcRII on PMN functions other than enzyme release and superoxide generation will also be investigated. These include chemotaxis, priming, and deactivation. Interactions of FcRII with other cell surface receptors, including other FcR, complement receptors, and those for beta glucan, mannosyl/fucosyl, formyl-peptide and fibronectin. Finally, factors which influence FcRII metabolism and expression on the cell surface will be studied. Preliminary data indicating that the receptor is rapidly internalized will be further explored, and the factors which influence cycling of receptors will be explored. Alterations in protein synthesis triggered by receptor signalling will be examined. The goal of the subproject is increased knowledge of the functioning of FcRII on PMN and the cell processes it governs.
