Resistance to nitric oxide by l. amazonensis and l. braziliensis and correlation with disease. / Resistência de l. braziliensis e l. amazonensis ao óxido nítrico e correlação com a doença.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2004

RESUMO

Macrophage activation by CD4 Th1 cells which produce IFN is one of the most important mechanism against Leishmania. This activation leads to release nitric oxide (NO), a toxic product for Leishmania parasites. The role of NO in protecting against Leishmania infection is well documented in murine macrophages but it is still not well disputed in human macrophages. NO is produced by inducible nitric oxide syntase (iNOS), that is activated synergically by IFN and TNF. The inhibition of iNOS from murine macrophage by D-arginina, results an increase parasite load and sloughing footpad. The existence of Leishmania naturally resistant to NO in vitro has not been documented. This work evaluated the toxicity of NO on viability of L. braziliensis and L. amazonensis isolated from patients with cutaneous, mucosal or disseminated leishmaniasis. Concentration from 8 mM of NaNO2 (NO donor) induced the death of 100% L. amazonensis and L. braziliensis promastigotes susceptible to NO, while the resistant counterparts survived in concentrations as high as 16mM NaNO2. Associating these data with initial skin lesion size, it was observed that patients infected with NO resistant Leishmania had larger skin lesion size (43, 18mm) than patients infected with NO susceptible (18, 8mm). Additionally, more isolates resistant than susceptible to NO were from patients with mucosal leishmaniasis. The ability of these NO resistant and susceptible Leishmania to infect human macrophages was compared and it was demonstrated that at 96 hours incubation resistant L. amazonensis and L. braziliensis presented higher capacity to infect and multiply within in human macrophages than their susceptible counterparts (p<0.05). Nitrite was lesser detected in supernatants from humans macrophages infected with NO resistant Leishmania (L. braziliensis = 0; L. amazonensis = 3M) than their susceptible counterparts (L. braziliensis = 12M; L. amazonensis = 7,6M) at 96 hours of infection. These data showed that both L. amazonensis and L. braziliensis can present susceptibility and resistance to NO, and that NO resistance can interfere in the clinical outcome of leishmaniasis.

ASSUNTO(S)

imunologia resistencia e susceptível nitric oxide l. amazonensis macrófagos l. braziliensis resistant human macrophages mtt leishmania amazonensis susceptible leishmania braziliensis óxido nítrico

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