Nitric oxide plays a key role in the platelet‐activating factor‐induced enhancement of resistance against systemic candidiasis

Abstract

SummaryPlatelet-activating factor (PAF) has been demonstrated to augment resistance against Candida albicans infection. In this study, the role of nitric oxide (NO) in PAF-induced resistance in the kidneys was investigated. Pretreatment of the C. albicans-infected mice with PAF resulted in strong expression of messenger RNA (mRNA) and the protein synthesis of inducible nitric oxide synthase (iNOS). These PAF effects were inhibited to a significant degree by pretreatment with the nuclear factor-jB inhibitor, pyrrolidinedithiocarbamate. Pretreatment with PAF protected the mice from death caused by C. albicans infection and reduced the growth of fungus in the kidneys. The protective activity of PAF was abrogated by pretreatment with the iNOS inhibitor, aminoguanidine, and in the iNOS )/) mice. The PAF markedly increased the infiltration of neutrophils, but not macrophages, and also enhanced the mRNA expression levels of the CXC chemokine, keratinocyte-derived chemokine, in C. albicansinfected kidneys. These effects of PAF were attenuated in the aminoguanidine-treated mice and the iNOS )/) mice. These data show that NO plays an important role in PAF-induced protection against C. albicans.

Dissecting the Mechanism of Intracellular Mycobacterium smegmatis Growth Inhibition by Platelet Activating Factor C-16

“…A number of previous studies have shown that exogenous PAF C-16 can inhibit the growth of intracellular pathogens, including Leishmania donovani (Lonardoni et al, 2000), Leishmania braziliensis (Borges et al, 2017), Trypanosoma cruzi (Aliberti et al, 1999), and Candida albicans (Im et al, 1997;Kim et al, 2008) in vivo as well as in vitro. PAF C-16 induced growth inhibition of these intracellular pathogens was shown to be associated with an enhanced production of ROIs, RNIs, and TNF-α.…”

“…Exogenous PAF C-16 has also been shown to inhibit the growth of intracellular pathogenic protozoans such as Leishmania and Trypanosoma inside human and mouse macrophages by causing the production of reactive oxygen and nitrogen species (Aliberti et al, 1999;Lonardoni et al, 2000;Borges et al, 2017). Similarly, administration of exogenous PAF C-16 in mice, infected with lethal doses of Candida albicans, reduced the number of pathogens and improved the survival via production of NO and TNF-α (Im et al, 1997;Kim et al, 2008).…”