Leishmania donovani attachment stimulates PKC-mediated oxidative events in bone marrow-derived macrophages

Anil K. Bhunia, Dwijen Sarkar, Pijush K. Das

Research output: Contribution to journalArticle

Abstract

We investigated activation signaling events in bone marrow-derived macrophages after infection with Leishmania donovani, an intracellular parasite of macrophages. Leishmania donovani infection caused a general suppression of activation parameters like O2 and NO production. However, conditions which allow parasite attachment and prevent entry resulted in triggering of O2 and NO production and stimulation of O2 consumption. Optimal NO and O2 production occurred when bone marrow derived macrophages and Leishmania ratio was 1:100. The activation signal for O2 production was initiated 15 min after parasite attachment, whereas augmentation of NO production started 6 h alter attachment. Activation of O2 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.

Original languageEnglish (US)
Pages (from-to)373-379
Number of pages7
JournalJournal of Eukaryotic Microbiology
Volume43
Issue number5
DOIs
StatePublished - Jan 1 1996

Keywords

  • Host-parasite interactions
  • nitrite
  • protein kinase C
  • superoxide

ASJC Scopus subject areas

  • Microbiology

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