Rijneveld Anita W, van den Dobbelsteen Germie P, Florquin Sandrine, Standiford Theodore J, Speelman Peter, van Alphen Loek, van der Poll Tom
Department of Experimental Internal Medicine, Tropical Medicine, and AIDS, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
J Infect Dis. 2002 Jan 1;185(1):123-6. doi: 10.1086/338008. Epub 2001 Nov 30.
Pneumolysin (PLY), a toxin synthesized by Streptococcus pneumoniae, is an important virulence factor in pneumococcal disease. This study evaluated the effects of PLY in lungs of mice. Intranasal inoculation with PLY was associated with a dose-dependent influx of polymorphonuclear leukocytes (PMNL) in bronchoalveolar lavage fluid (BALF) and increased concentrations of interleukin (IL)-6, macrophage inflammatory protein (MIP)-2, and KC in BALF. PLY mutants with either reduced cytolytic activity or reduced cytolytic and complement-activating activities were less potent in inducing PMNL recruitment to the lung (P<.05), which suggests that PLY cytolytic activity is very important for the inflammatory response. IL-6 and MIP-2 also played a role in PLY-induced PMNL recruitment; this response was partially diminished in IL-6 gene-deficient mice and in mice treated with anti-MIP-2 antiserum. PLY may play an important role in the induction of an inflammatory response in the pulmonary compartment in the early phase of pneumococcal pneumonia.
肺炎溶血素（PLY）是肺炎链球菌合成的一种毒素，是肺炎球菌疾病中的重要毒力因子。本研究评估了PLY对小鼠肺部的影响。经鼻接种PLY与支气管肺泡灌洗液（BALF）中多形核白细胞（PMNL）的剂量依赖性流入以及BALF中白细胞介素（IL）-6、巨噬细胞炎性蛋白（MIP）-2和KC浓度升高有关。细胞溶解活性降低或细胞溶解及补体激活活性降低的PLY突变体在诱导PMNL向肺部募集方面效力较低（P<0.05），这表明PLY细胞溶解活性对炎症反应非常重要。IL-6和MIP-2在PLY诱导的PMNL募集中也起作用；在IL-6基因缺陷小鼠和用抗MIP-2抗血清处理的小鼠中，这种反应部分减弱。PLY可能在肺炎球菌肺炎早期肺部炎症反应的诱导中起重要作用。
