Ligation of Fc receptor of macrophages stimulates protein kinase C and anti-leishmanial activity.
Fc receptors are known to express on the surface of mature monocytes, macrophages and lymphocytes. In this study a ligand e.g. liposomal IgG (human IgG coupled to PE-liposome via carbodimide reaction) was developed to ligate the Fc receptor of macrophages. When liposomal IgG was incubated with macrophages at 37 degrees C for 5 min, it induced the macrophage activation which suppress the parasite burden approximately to an extent of 60%, 50% and 45%, when macrophages were infected with UR6, AG83 and GE1 strains of L-donovani 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 macrophage membrane fraction, suggesting its translocation from the cytosol. Staurosporine, a potent inhibitor of the enzyme protein kinase C (PKC) has been found to protect the parasite inside the macrophage indicating the role of PKC in the signaling process. The liposomal IgG treatment has been found to induce the generation of significant amount of superoxide and hydrogen peroxide which helped to suppress the parasite burden. Further when liposomal IgG were incubated with IFN-gamma primed, LPS activated macrophages, a significant amount of NO release was also noticed, indicating its role in parasite killing. The above results suggest that Fc receptor mediated activation by liposomal IgG may be used as an alternative approach to kill parasites intracellularly.
Dasgupta
D
D
Biomembrane Division, Indian Institute of Chemical Biology, Calcutta, India.
Chakraborty
P
P
Basu
M K
MK
D000818:Animals; D002478:Cells, Cultured; D004337:Drug Carriers; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology; D007893:Leishmania donovani / Q000472:pathogenicity / Q000502:physiology*; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011961:Receptors, Fc / Q000276:immunology / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004337:Drug Carriers; D007074:Immunoglobulin G; D008081:Liposomes; D011961:Receptors, Fc; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate