The involvement of nitric oxide in the anti‐Candida albicans activity of rat neutrophils

Abstract

SUMMARY Rat peritoneal neutrophils (PMN) spontaneously release nitric oxide (NO) when incubated in vitro.Addition of the NO synthase inhibitor L-monomethylarginine (L-NMMA) to the PMN reduces NO production and impairs the killing of the yeast Candida albicans, both effects being reversed by Larginine. These data strongly suggest that oxidative metabolism of L-arginine by PMN is involved in the candidacidal activity of these cells. Rat blood PMN, which do not produce significant amounts of NO, exhibit a reduced killing capacity compared with peritoneal cells, except when they are obtained from lipopolysaccharide (LPS)-treated rats. In this case they produce measurable amounts of nitrite and express high fungicidal activity in vitro. Confirming the candidacidal activity of NO, the exposure of the C. albicans cultures to different concentrations of NO donors leads to a reduction in their survival. The candidacidal activity related to the NO pathway in rat PMN is phagocytosis dependent, since the activity can be inhibited by cytochalasin B. However, the oxidative products of oxygen released by rat PMN do not seem to be involved in their candidacidal activity, as incubation of the cells with phorbol myristate acetate (PMA) increases release of superoxide anion but does not affect the pattern of killing. Our results suggest that NO could be an important candidacidal pathway in rat neutrophils.

Nitric oxide mediates the microbicidal activity of eosinophils

“…An important protective role for reactive nitrogen intermediates has been established in macrophage killing of intracellular protozoa (Liew & Millott 1990, Adams et al 1990, Vincendeau & Dalouede 1991, Gazzinelli et al 1992, bacteria (Adams et al 1991, Denis 1991, fungus (Cenci et al 1993) and virus (Gunasegaran et al 1993). A similar role has also been demonstrated in neutrophil killing of C. albicans (Fierro et al 1996) and Staphilococcus aureus (Malawista et al 1992). Since there are data showing that eosinophils are able to kill Leishmania (Pimenta et al 1987, Pearson et al 1987, we investigated whether NO mediates the killing of this intracellular parasite by stimulated eosinophils.…”

“…Recently, it was demonstrated that the microbicidal activity of neutrophils against C. albicans is also mediated by NO (Fierro et al 1996).…”

TNF‐α mediates the induction of nitric oxide synthase in macrophages but not in neutrophils in experimental cutaneous leishmaniasis

“…Despite demonstrations that L. major is able to infect neutrophils ([14] and present results) and that these cells are involved in the control of infection caused by L. major [14], L. amazonensis [19] and L. infantum [13], as well as by other parasites such T. gondii [20], the mechanism involved in the neutrophil-mediated killing of L. major has not been shown. The fact that neutrophils kill microorganisms such as Candida albicans by a mechanism dependent on NO production [21] and the presence of neutrophils expressing iNOS in the lesion of L. major-infected mice suggest that these cells might be involved in the control of parasite growth in the anti-TNF- § -treated mice by a mechanism dependent on NO production. However, it is important to point out that there is also controversy about C57BL/6 mice concerning the participation of neutrophils in the control of L. major infection.…”

Induction of NOS in rat blood PMN in vivo and in vitro: modulation by tyrosine kinase and involvement in bactericidal activity

“…We recently demonstrated that NO is involved in the candidacidal activity of rat inflammatory peritoneal neutrophils [15] and other authors have shown that NO contributes to the tumoricidal activity of those cells [16]. In addition, the NO-generating system in neutrophils has been suggested to function as an autocrine mechanism that may regulate PMN activation during various pathophysiological conditions in vivo [17].…”