Im S Y, Choi J H, Ko H M, Han S J, Chun S B, Lee H K, Ha T Y
Department of Microbiology, College of Natural Sciences, Chonnam National University, Kwangju, Republic of Korea.
Infect Immun. 1997 Apr;65(4):1321-6. doi: 10.1128/iai.65.4.1321-1326.1997.
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.
血小板活化因子（PAF）是一种由磷脂衍生的强效免疫和炎症过程调节剂。在本研究中，对外源性和内源性PAF在抵抗白色念珠菌感染中的作用进行了研究。在白色念珠菌致死性攻击后给予PAF可显著保护小鼠免于死亡，并减少肾脏中的菌量。用PAF拮抗剂BN50739中和内源性PAF会缩短平均存活时间，并增加每个肾脏中白色念珠菌细胞的数量。小鼠感染后不久（30分钟），血清中检测到显著水平的PAF。PAF诱导的保护作用似乎是通过肿瘤坏死因子α（TNF-α）的作用介导的，因为在每次注射PAF之前用抗TNF-α进行预处理可消除大部分PAF诱导的增强抵抗力。体内给予PAF可提高血清TNF-α水平以及肾脏中TNF-α mRNA的表达。在白色念珠菌感染之前用PAF拮抗剂BN50739进行预处理可显著减少TNF-α的产生。我们得出结论，在白色念珠菌感染期间产生的PAF在决定对这种感染性微生物的抵抗水平方面发挥着重要作用。PAF的这种作用似乎至少部分是通过诱导TNF-α介导的。
