Cyclic AMP mediates change in superoxide dismutase activity to monitor host-parasite interaction in Leishmania donovani.
The present study is designed to understand the role of cyclic AMP (cAMP) in host-parasite interaction involving Leishmania donovani, the causative agent for Kala-azar. When Leishmania promastigotes or macrophages were pretreated with dibutyryl cAMP or theophylline and epinephrine, which are well defined initiators for cAMP release, a key enzyme of the oxygen defense system, superoxide dismutase (SOD), was inhibited. At the same time, parasite interaction was considerably reduced to the level of 54.5% and 46.2%, respectively, for pretreated promastigotes. Internalization of the organisms in phagolysosomes was similarly affected. Dibutyryl cAMP-treated promastigotes in the presence of SOD, on the other hand, restored in vitro infection to the normal level. At least 50% less cAMP entered into Leishmania promastigotes when SOD was added to the incubation system containing dibutyryl cAMP. Data reveal that cAMP perturbs the Leishmania-macrophage interaction through inhibition of SOD, pointing to the importance of a promastigote enzyme for the survival of this pathogen within phagolysosomes.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology; D006790:Host-Parasite Interactions; D007893:Leishmania donovani / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D003994:Bucladesine; D013806:Theophylline; D000242:Cyclic AMP; D013482:Superoxide Dismutase; D004837:Epinephrine