A protective role of platelet-activating factor in murine candidiasis.
Platelet-activating factor (PAF) is a potent phospholipid-derived modulator of immunological and inflammatory processes. In this study, the role of exogenous and endogenous PAF in resistance to infection with Candida albicans was investigated. Administration of PAF following a lethal challenge of C. albicans significantly protected mice from death and reduced the number of organisms in the kidneys. Neutralization of endogenous PAF with the PAF antagonist BN50739 shortened the mean survival time and increased the number of C. albicans cells per kidney. Shortly after infection of mice (30 min), significant levels of PAF were detected in the serum. PAF-induced protection appears to be mediated through the actions of tumor necrosis factor alpha (TNF-alpha), since pretreatment with anti-TNF-alpha before each injection of PAF abrogated the majority of PAF-induced enhanced resistance. Administration of PAF in vivo elevated serum TNF-alpha levels and TNF-alpha mRNA expression in the kidney. Production of TNF-alpha was markedly diminished by pretreatment with the PAF antagonist BN50739 prior to infection with C. albicans. We conclude that PAF, which is produced during infection with C. albicans, plays an important role in determining the level of resistance to this infectious microorganism. This effect of PAF appears to be mediated, at least in part, through the induction of TNF-alpha.
Im
S Y
SY
Department of Microbiology, College of Natural Sciences, Chonnam National University, Kwangju, Republic of Korea.
Choi
J H
JH
Ko
H M
HM
Han
S J
SJ
Chun
S B
SB
Lee
H K
HK
Ha
T Y
TY
D000818:Animals; D002177:Candidiasis / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010972:Platelet Activating Factor / Q000008:administration & dosage* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D010972:Platelet Activating Factor; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha