FC-GAMMA RECEPTOR-MEDIATED REGULATION OF MACROPHAGE

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The overall objective of the work is to elucidate the molecular mechanism of cell-cell and intracellular communications that are triggered by the specific binding of the immunoglobulin G to Fc-gamma receptors (Fc-gamma-R) present on the surface of B cells, macrophages, and other cell types. The specific aims are to: (1) determine the nature of an initial biochemical signal transmitted by Fc-gamma-Rs on the surface of murine macrophages and macrophage-cell lines and (2) investigate the biochemical sequence of events following the initial signal transmitted by the Fc-Fc-gamma-R interaction. These goals will be approached by: (1) isolation and characterization of Fc-gamma-Rs, phospholipase A2, adenylate cyclases, and cAMP-dependent protein kinases and (2) studies of Fc-gamma-R-triggered cyclooxygenase and lipooxygenase pathways, cAMP synthesis, and activation of cAMP-dependent protein kinases at the cell level. The results obtained should contribute to the understanding of the biochemical basis for the cellular interactions that play important roles in the immune response in general. (CS)