Macrophages express a cell surface receptor which binds and internalizes glycoproteins and oligosaccharides terminating in mannose or fucose. Liver and blood plasma contain a mannose-binding protein (32 K) which has a sugar-specificity similar to, if not identical, with the macrophage mannose receptor. The work outlined in this proposal will focus on determining the relationship between the mannose receptor and the mannose-binding protein. The receptor will be isolated and characterized and antibody to the receptor will be used to undertake biosynthetic experiments. In detail, the presence of an intracellular precursor and secretory form of the receptor will be explored. The mannose receptor is regulated by the action of macrophage activity factor and anti-inflammatory steroids. The former may involve an intracellular mediator, the latter appears to involve metabolites of arachidonic acid and prostaglandins. The modulation of the expression of the mannose-receptor will be studied in some detail. The possible immunologic and physiologic functions of the mannose receptor and mannose binding protein will be studied-specifically with respect to the uptake of mannosylated organisms by macrophages and whether the mannose binding protein plays some role in the adherence of certain bacteria (e.g., E. coli which carry mannose lectins) to the surface of cells. A possible role of the mannose binding protein in triggering T-lymphocytes to secrete macrophage activation factor will be evaluated. Finally, drug ligand complexes will be made with high mannose oligosaccharides to target drugs to macrophages which harbor infectious organisms such as Leishmania.