INVESTIGADORES
GAMBERALE Romina
artículos
Título:
Effect of nitric oxide donors on oxygen-dependent cytotoxic responses mediated by neutrophils
Autor/es:
ANDONEGUI GRACIELA; TREVANI ANALIA; GAMBERALE ROMINA; CARRERAS MC; PODEROSO JJ; GIORDANO MIRTA; GEFFNER JORGE
Revista:
JOURNAL OF IMMUNOLOGY
Editorial:
AMER ASSOC IMMUNOLOGISTS
Referencias:
Año: 1999 vol. 162 p. 2922 - 2930
ISSN:
0022-1767
Resumen:
We analyzed the effect of nitric oxide
(NO) on oxygen-dependent cytotoxic responses mediated by neutrophils
against unopsonized erythrocytes using three NO donors:
S-nitrosoglutathione (GSNO), S-nitroso-N-acetylpenicillamine (SNAP), and
sodium nitroprusside (SNP). Neutrophils were treated with these
compounds for 1-2 min at 37 degrees C and cytotoxicity was then
triggered in the presence of NO donors by precipitating immune
complexes, aggregated IgG, the chemotactic peptide FMLP, or opsonized
zymosan. GSNO induced, in all cases, a marked increase in cytotoxic
responses, while SNAP moderately increased cytotoxicity triggered by
immune complexes, aggregated IgG, or Z, opsonized zymosen, without
modifying those responses induced by FMLP. By contrast, SNP dramatically
suppressed cytotoxicity triggered by all of the stimuli assessed. The
enhancing effects mediated by GSNO and SNAP did not depend on the
stimulation of guanylyl cyclase and were prevented by the NO scavengers
hemoglobin and PTIO (2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl
3-oxide). The inhibitory activity of SNP, on the other hand, was not
prevented by NO scavengers, suggesting that it cannot be ascribed to the
release of NO. In another set of experiments, neutrophils were
pretreated with GSNO or SNAP for different times. Then cells were washed
to remove NO donors from the culture medium, and cytotoxicity was
triggered by different stimuli. It was found that neutrophils must be
pretreated with NO donors for at least 4 h to increase cytotoxic
responses, and pretreatment for longer periods (i.e., 8 or 18 h) further
increased cytotoxicity. Not only cytotoxic responses, but also the
production of O2- and H2O2, and the release of myeloperoxidase were
increased under these conditions.