Nitric oxide plays a key role in the platelet-activating factor-induced enhancement of resistance against systemic candidiasis.
Platelet-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-kappaB 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. albicans-infected 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.
Kim
Han-A
HA
Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Gwangju, Korea. kha1009@hanmail.net
Kim
So-Hee
SH
Ko
Hyun-Mi
HM
Choi
Jung-Hwa
JH
Kim
Kyoung-Jin
KJ
Oh
Sin-Hye
SH
Cho
Kyoung-Oh
KO
Choi
Il-Whan
IW
Im
Suhn-Young
SY
D000818:Animals; D002176:Candida albicans / Q000254:growth & development; D002177:Candidiasis / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D007668:Kidney / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010972:Platelet Activating Factor / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D006146:Guanidines; D016328:NF-kappa B; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine