Effect of recombinant Panton-Valentine leukocidin in vitro on apoptosis and cytokine production of human alveolar macrophages
Effect of recombinant Panton-Valentine leukocidin in vitro on apoptosis and cytokine production of human alveolar macrophages
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DOI：
10.1139/w10-002
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发表时间：
2010-03-01
影响因子：
2.8
通讯作者：
Zhang, Tiantuo
中科院分区：
文献类型：
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作者：
Wu, Benquan;Zhang, Wenxian;Zhang, Tiantuo
Panton Valentine杀白细胞素（PVL）与发生在其他健康个体中的坏死性肺炎的罕见病例有关。人肺泡巨噬细胞（HAM）是宿主防御感染的主要效应细胞。然而，PVL对HAM的影响是不确定的。我们评估了PVL在细胞毒性和HAM分泌的炎性细胞因子产生中的作用。从支气管肺泡灌洗液中纯化HAM。重组PVL（rPVL）在研究中用于干扰HAM凋亡和细胞因子的产生。Hoechst 33342荧光染色、透射电镜观察和流式细胞仪检测结果表明，rPVL（10 nmol/L）处理后HAM具有明显的凋亡特征，而rPVL（100 nmol/L）处理后HAM具有明显的坏死特征。相对于未处理的对照细胞，10 nmol/L的rPVL处理引起HAM分泌IL-10，但肿瘤坏死因子（TNF）-α的组成性分泌略有下降。我们的研究结果表明，PVL处理的样品降低了HAM的活力，导致细胞凋亡在低浓度和坏死在高浓度。此外，PVL处理的细胞释放的IL-10的量增加，TNF-α的量减少，在凋亡诱导浓度下。因此，我们推测PVL可能在较低浓度下对HAM功能起负面作用。
Panton Valentine leukocidin (PVL) is associated with rare cases of necrotizing pneumonia that occur in otherwise healthy individuals. Human alveolar macrophages (HAMs) are major effector cells in host defense against infections. However, the impact of PVL on HAMs is uncertain. We evaluated the role of PVL in cytotoxicity and production of inflammatory cytokines secreted by HAMs. HAMs were purified from bronchoalveolar lavage fluid. Recombinant PVL (rPVL) was used in the study to interfere with HAM apoptosis and cytokine production in vitro. Hoechst 33342 fluorescence staining, transmission electron microscopy examination, and flow cytometry indicated that rPVL (10 nmol/L) treatment resulted in HAMs with markedly apoptotic characteristics, and HAMs treated with rPVL at 100 nmol/L showed clear indication of necrosis. A treatment of rPVL at 10 nmol/L elicited the secretion of IL-10 by HAMs relative to untreated control cells, but there was a slight decrease in the constitutive secretion of tumor necrosis factor (TNF)-alpha. Our results indicate that PVL-treated samples decreased HAM viability, leading to apoptosis at low concentrations and necrosis at high concentrations. In addition, PVL-treated cells released increased amounts of IL-10 and decreased amounts of TNF-alpha under apoptosis-inducing concentrations. Therefore, we speculated that PVL could play a negative role in HAM function at lower concentrations.