TNF-alpha activates human monocytes for Paracoccidioides brasiliensis killing by an H2O2-dependent mechanism.
Human monocytes activated by recombinant tumor necrosis factor alpha (TNF-alpha) exhibited significant fungicidal activity on the yeast cells of a highly virulent strain of Paracoccidioides brasiliensis. This process was significantly inhibited in the presence of catalase (CAT - a scavenger of H2O2), but not in the presence of superoxide-dismutase (SOD - a scavenger of superoxide anion) or NG-monomethyl-L-arginine (NG-MMLA - a nitric oxide inhibitor). Furthermore, there was a direct association between the intracellular killing of the fungus and the production of H2O2 by activated cells. These results strongly suggest a role for H2O2 in the killing of highly virulent strains of P. brasiliensis by TNF-alpha-activated human monocytes.
Carmo
J P M
JP
Department of Microbiology and Immunology, São Paulo State University (UNESP), Botucatu, SP, Brazil.
Dias-Melicio
L A
LA
Calvi
S A
SA
Peraçoli
M T S
MT
Soares
A M V C
AM
D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D016260:Monocytes, Activated Killer / Q000276:immunology* / Q000378:metabolism; D010228:Paracoccidioides / Q000187:drug effects* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide