Ligation of Fc receptor of macrophages stimulates protein kinase C and antileishmanial activity

Fc receptors are known to express on the surface of mature monocytes macrop hages and lymphocytes. In this study a ligand e.g. liposomal IgG (human IgG coupled to PE-liposome via carbodimide reaction) was developed to ligate t he Fc receptor of macrophages. When liposomal IgG was incubated with macrop hages at 37 degrees C for 5 min, it induced the macrophage activation which suppress the parasite burden approximatley to an extent of 60%, 50% and 45 %, when macrophages were infected with UR6, AG83 and GE1 strains of L-donov ani respectively. Superior efficacy of liposomal IgG were achieved compared to the treatment with free IgG and free liposomes. The activity of protein kinase C (PKC) has been found to be higher in the Fc receptor targeted mac rophage membrane fraction, suggesting its translocation from the cytosol. S taurosporine, a potent inhibitor of the enzyme protein kinase C (PKC) has b een found to protect the parasite inside the macrophage indicating the role of PKC in the signaling process. The liposomal IgG treatment has been foun d to induce the generation of significant amount of superoxide and hydrogen peroxide which helped to suppress the parasite burden. Further when liposo mal IgG were incubated with IFN-gamma primed, LPS activated macrophages, a significant amount of NO release was also noticed, indicating its role in p arasite killing. The above results suggest that Fc receptor mediated activa tion by liposomal IgG may be used as an alternative approach to kill parasi tes intracellularly.