fMLP receptor stimulated activation of macrophage: its effect on killing of intracellular Leishmania donovani.
The fMLP receptor of peritoneal macrophages stimulated by fMLP grafted liposomes as ligand, was analysed and compared with respective controls for its ability to promote killing of intracellular Leishmania parasites. fMLP grafted liposomes show greater efficacy in killing intracellular L. donovani (MHOM/IN/1983/AG83) parasites in a time dependent manner than free fMLP. fMLP grafted liposomes also release more active oxygen intermediates and reactive nitrogen intermediates (O2-, H2O2, NO) than free fMLP. The key enzymes PKC and PTK for the respiratory burst and nitric oxide generation were found to be important in this fMLP receptor mediated signaling process as the enzyme specific inhibitors viz. staurosporine, genistein and AG126 suppressed the leishmanicidal effect of fMLP grafted liposomes. The above findings suggest that the fMLP receptor of macrophages activates PKC and PTK mediated signalling that is responsible for the intracellular parasite killing.
Dasgupta
D
D
Biomembrane Division, Indian Institute of Chemical Biology, Jadavpur, Calcutta, Indian.
Chakraborty
P
P
Basu
M K
MK
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D007893:Leishmania donovani / Q000187:drug effects* / Q000472:pathogenicity; D008081:Liposomes; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000737:chemistry / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D018000:Receptors, Peptide / Q000187:drug effects / Q000378:metabolism*
D000981:Antiprotozoal Agents; D008081:Liposomes; D017382:Reactive Oxygen Species; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D009569:Nitric Oxide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C