Staphylococcal Panton-Valentine leukocidin induces pro-inflammatory cytokine production and nuclear factor-kappa B activation in neutrophils.
Staphylococcal Panton-Valentine leukocidin induces pro-inflammatory cytokine production and nuclear factor-kappa B activation in neutrophils.
复制标题
DOI：
10.1371/journal.pone.0034970
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yu F
中科院分区：
文献类型：
--
作者：
Ma X;Chang W;Zhang C;Zhou X;Yu F
Panton-Valentine杀白细胞素（PVL）是由金黄色葡萄球菌分泌的一种细胞毒素，与严重的坏死性感染有关。PVL靶向多形核白细胞，尤其是中性粒细胞，其是抵抗感染的第一道防线。虽然PVL可通过坏死或凋亡诱导中性粒细胞死亡，但中性粒细胞对该毒素的特异性炎症反应尚不清楚。在本研究中，体内和体外研究均表明，重组PVL在人中性粒细胞中具有重要的细胞毒性作用，在低浓度下导致细胞凋亡，在高浓度下导致坏死。重组PVL还增加了中性粒细胞的促炎细胞因子分泌水平。PVL可诱导核因子-κ B（NF-κB）活化，从而上调促炎细胞因子的表达。此外，阻断NF-κB可抑制炎性细胞因子的产生。为了检测中性粒细胞免疫应答在PVL诱导的急性肺损伤发病机制中的作用，我们使用免疫活性或免疫缺陷的兔建立坏死性肺炎模型。免疫功能正常的兔用PVL激发，表现出炎症增加，含有嗜中性粒细胞浸润。此外，肺组织匀浆中炎性细胞因子（IL-6、IL-8、TNF-α和IL-10）和NF-κB水平升高。与此相反，从肺组织中含有轻度或中度炎症，炎症细胞因子和NF-κB的水平只有轻微的增加。目前研究的数据支持越来越多的证据表明，中性粒细胞在PVL诱导的组织损伤和炎症的发病机制中起重要作用。PVL可刺激中性粒细胞释放促炎介质，从而引起急性炎症反应。PVL诱导炎性细胞因子释放的能力可能与NF-κB的活化或其成孔特性有关。
Panton-Valentine leukocidin (PVL) is a cytotoxin secreted by Staphylococcus aureus and associated with severe necrotizing infections. PVL targets polymorphonuclear leukocytes, especially neutrophils, which are the first line of defense against infections. Although PVL can induce neutrophil death by necrosis or apoptosis, the specific inflammatory responses of neutrophils to this toxin are unclear. In this study, both in vivo and in vitro studies demonstrated that recombinant PVL has an important cytotoxic role in human neutrophils, leading to apoptosis at low concentrations and necrosis at high concentrations. Recombinant PVL also increased the levels of pro-inflammatory cytokine secretion from neutrophils. The up-regulation of pro-inflammatory cytokines was due to nuclear factor-kappa B (NF-κB) activation induced by PVL. Moreover, blocking NF-κB inhibited the production of inflammatory cytokines. To test the role of neutrophil immune responses during the pathogenesis of PVL-induced acute lung injury, we used immunocompetent or neutropenic rabbits to develop a model of necrotizing pneumonia. Immunocompetent rabbits challenged with PVL demonstrated increased inflammation containing neutrophilic infiltrates. In addition, there were elevated levels of inflammatory cytokines (IL-6, IL-8, TNF-α and IL-10) and NF-κB in the lung homogenate. In contrast, the lung tissues from neutropenic rabbits contained mild or moderate inflammation, and the levels of inflammatory cytokines and NF-κB increased only slightly. Data from the current study support growing evidence that neutrophils play an important role in the pathogenesis of PVL-induced tissue injury and inflammation. PVL can stimulate neutrophils to release pro-inflammatory mediators, thereby causing an acute inflammatory response. The ability of PVL to induce inflammatory cytokine release may be associated with the activation of NF-κB or its pore-forming properties.
登录
查看更多内容
DOI：
10.1073/pnas.0409650102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Boehning, D;van Rossum, DB;Snyder, SH
通讯作者：
Snyder, SH
影响因子：
14.6
作者：
Gilbert, Mark;MacDonald, Judy;Conly, John
通讯作者：
Conly, John
影响因子：
2.8
作者：
Wu, Benquan;Zhang, Wenxian;Zhang, Tiantuo
通讯作者：
Zhang, Tiantuo
影响因子：
15.9
作者：
Genestier, AL;Michallet, MC;Genestier, L
通讯作者：
Genestier, L
影响因子：
3.1
作者：
Montgomery, Christopher P.;Daum, Robert S.
通讯作者：
Daum, Robert S.