Leishmania donovani Attachment Stimulates PKC-Mediated Oxidative Events in Bone Marrow-Derived Macrophages
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Leishmania donovani Attachment Stimulates PKC-Mediated Oxidative Events
in Bone Marrow-Derived Macrophages
Bhuniya, Anil K
Das, Pijush K
Infectious Diseases and Immunology
We investigated activation signaling events in bone marrow-derived macrophages after infection with Leishmania dono-
vani, an intracellular parasite of macrophages. Leishmania donovani infection caused a general suppression of activation parameters like
02- and NO production. However, conditions which allow parasite attachment and prevent entry resulted in triggering of 0,- and NO
production and stimulation of 0, consumption. Optimal NO and 0,- production occurred when bone marrow-derived macrophages and
Leishmania ratio was 1:lOO. The activation signal for 0,- production was initiated 15 min after parasite attachment, whereas augmentation
of NO production started 6 h after attachment. Activation of 0,- and NO generation by L. donovani attachment was inhibited by
staurosporine as well as by prolonged treatment of phorbol myristate acetate suggesting a protein kinase C-dependent mechanism.
Translocation studies showed that protein kinase C activity in cell membrane fraction rapidly and transiently increased following parasite
attachment. No such protein kinase C translocation event occurred in L. donovani infected bone marrow-derived macrophages. Phorbol
myristate acetate was found to stimulate membrane translocation of protein kinase C in parasite attached cells whereas it was impaired
in infected cells. However, both attachment and infection induced a similar shift of phorbol receptors from cytosolic to membrane fraction
indicating that in infected cells the translocation of protein kinase C protein was not impaired but the activity of the membrane associated
enzyme was somehow inhibited. These results suggest that although internalization of intracellular parasites like L. donovani caused
inhibition of nitrite and superoxide release, mere attachment on macrophage surface resulted in an activation of protein kinase C-mediated
downstream oxidative events.
Bhuniya, Anil K and Sarkar, Dwijen and Das, Pijush K (1996) Leishmania donovani Attachment Stimulates PKC-Mediated Oxidative Events in Bone Marrow-Derived Macrophages. Journal of Euk. Microbiology, 43 (5). pp. 373-379.