Leishmania mexicana lipophosphoglycan differentially regulates PKCα-induced oxidative burst in macrophages of BALB/c and C57BL/6 mice

Leishmania are protozoan parasites that infect macrophages and their survival is partially achieved through inhibition of the cellular oxidative burst by parasite lipophosphoglycan (LPG). PKC alpha is the predominant PKC isoenzyme required for macrophage oxidative burst, yet it is not known if different susceptibility of BALB/c and C57BL/6 mice to Leishmania mexicana could be related to PKC alpha. We analysed the effect of L. mexicana promastigotes and parasite LPG on expression of PKC alpha and on its activity in macrophages of both mouse strains. Our data show that expression of the isoenzyme was not altered either by LPG or by L. mexicana promastigotes. Yet LPG exerted opposing effects on PKC alpha activity of macrophages between both strains: in susceptible BALB/c cells, it inhibited PKC alpha activity, whereas in the more resistant strain it augmented enzymatic activity 2 8 times. In addition, LPG inhibited oxidative burst only in susceptible BALB/c macrophages and the degree of inhibition correlated with parasite survival. Promastigotes also inhibited PKC alpha activity and oxidative burst in macrophages of BALB/c mice, whereas in C57BL/6, they enhanced PKC alpha activity and oxidative burst inhibition was less severe. Our data indicate that control of PKC alpha-induced oxidative burst by L. mexicana LPG relates with its success to infect murine macrophages.