Staphylococcus aureus Beta-Toxin Induces Lung Injury through Syndecan-1
Staphylococcus aureus Beta-Toxin Induces Lung Injury through Syndecan-1
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DOI：
10.2353/ajpath.2009.080394
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发表时间：
2009-02-01
影响因子：
6
通讯作者：
Park, Pyong Woo
中科院分区：
文献类型：
--
作者：
Hayashida, Atsuko;Bartlett, Allison H.;Park, Pyong Woo
在由细菌金黄色葡萄球菌引起的肺炎中，由这种感染引发的强烈炎症反应可导致肺损伤的发展。然而，关于特定毒力因子对这种炎症、疾病的影响知之甚少，这种炎症、疾病导致显著的死亡率和发病率。在这项研究中，我们研究了β毒素，一种中性鞘磷脂酶，在S。金色引起的肺损伤。我们的研究结果表明，肺损伤的主要特征-特别是嗜酸性炎症增加，血清蛋白质血管渗漏到肺组织中，以及蛋白质渗出到气道中-在鼻内感染S的小鼠中显著减弱。金黄色葡萄球菌β-毒素缺陷的小鼠与感染金黄色葡萄球菌的小鼠相比。表达P-毒素的金黄色葡萄球菌。此外，鼻内给予β-毒素在野生型小鼠中诱发肺损伤的特征性特征，而β-毒素缺乏症小鼠受到保护免于这种损伤。然而，缺乏鞘磷脂酶活性的突变型β毒素小鼠未能触发肺损伤的特征。鞘磷脂酶活性的消融也干扰了β-毒素刺激多配体蛋白聚糖-1（一种在上皮细胞中发现的主要硫酸乙酰肝素蛋白聚糖）的胞外域脱落的能力。此外，与野生型小鼠相比，syndecan-1-null小鼠显著免受β-毒素诱导的肺损伤。这些数据表明S.金黄色葡萄球菌β-毒素是通过其鞘磷脂酶活性和多配体蛋白聚糖-1诱导嗜中性粒细胞介导的肺损伤的关键毒力因子。(Am J Pathol 2009，174：509-518; DOI：10.2353/ajpath.2009.080394）
In pneumonia caused by the bacterium Staphylococcus aureus, the intense inflammatory response that is triggered by this infection can lead to the development of lung injury. Little is known, however, about the impact of specific virulence factors on this inflammation, disorder, which causes both significant mortality and morbidity. In this study, we examined the role of beta-toxin, a neutral sphingomyelinase, in S. aureus-induced lung injury. Our results showed that the central features of lung injury-specifically, increased neutrophilic inflammation, vascular leakage of serum proteins into the lung tissue, and exudation of proteins into the airway-are significantly attenuated in mice infected intranasally with S. aureus deficient in beta-toxin compared with mice infected with S. aureus expressing P-toxin.. in addition, intranasal administration of beta-toxin evoked the characteristic features of lung injury in wild-type mice whereas neutropenic mice were protected from such injury. However, mutant beta-toxin mice deficient in sphingomyelinase activity failed to trigger features of lung injury. Ablation of sphingomyelinase activity also interfered with the ability of beta-toxin to stimulate ectodomain shedding of syndecan-1, a major heparan sulfate proteoglycan found in epithelial cells. Moreover, syndecan-1-null mice were significantly protected from beta-toxin-induced lung injury relative to wild-type mice. These data indicate that S. aureus beta-toxin is a critical virulence factor that induces neutrophil-mediated lung injury through both its sphingomyelinase activity and syndecan-1. (Am J Pathol 2009, 174:509-518; DOI: 10.2353/ajpath.2009.080394)