Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae.
Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae.
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DOI：
10.1016/j.jaci.2015.06.033
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Grigg J
中科院分区：
文献类型：
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作者：
Suri R;Periselneris J;Lanone S;Zeidler-Erdely PC;Melton G;Palmer KT;Andujar P;Antonini JM;Cohignac V;Erdely A;Jose RJ;Mudway I;Brown J;Grigg J
电焊工患肺炎球菌肺炎的风险增加。这种关联的机制尚不清楚。肺炎球菌粘附和感染下呼吸道细胞的能力由宿主表达的血小板活化因子受体（PAFR）介导。我们试图评估低碳钢焊接烟雾（MS-WF）对PAFR依赖性肺炎球菌粘附和感染体外人气道细胞的影响，以及对小鼠模型中肺炎球菌气道感染的影响。通过它们在体外减少抗氧化剂的能力来评估MS-WF的氧化潜力。通过定量细菌培养评估A549、BEAS-2B和原代人支气管气道细胞的肺炎球菌粘附和感染，并表示为菌落形成单位（CFU）。鼻内滴注MS-WF后，小鼠感染肺炎链球菌，并测定支气管肺泡灌洗液（BALF）和肺CFU值。采用免疫荧光和免疫组织化学方法检测PAFR蛋白水平，采用定量PCR方法检测PAFR mRNA表达。PAFR被CV-3988阻断，氧化应激被N-乙酰半胱氨酸减弱。结果：MS-WF具有较高的氧化电位。在A549和BEAS-2B细胞中，MS-WF增加肺炎球菌粘附和感染以及PAFR蛋白表达。CV-3988和N-乙酰半胱氨酸均降低了MS-WF刺激的肺炎球菌粘附和气道细胞感染。MS-WF增加小鼠肺PAFR mRNA表达，并增加BALF和肺肺炎球菌CFU值。在MS-WF暴露小鼠中，CV-3988降低了BALF CFU值。焊工对肺炎球菌肺炎的过敏性部分是由焊接烟雾增加PAFR依赖性肺炎球菌粘附和下气道细胞感染的能力介导的。
Welders are at increased risk of pneumococcal pneumonia. The mechanism for this association is not known. The capacity of pneumococci to adhere to and infect lower airway cells is mediated by host-expressed platelet-activating factor receptor (PAFR). We sought to assess the effect of mild steel welding fumes (MS-WF) on PAFR-dependent pneumococcal adhesion and infection to human airway cells in vitro and on pneumococcal airway infection in a mouse model. The oxidative potential of MS-WF was assessed by their capacity to reduce antioxidants in vitro. Pneumococcal adhesion and infection of A549, BEAS-2B, and primary human bronchial airway cells were assessed by means of quantitative bacterial culture and expressed as colony-forming units (CFU). After intranasal instillation of MS-WF, mice were infected with Streptococcus pneumoniae, and bronchoalveolar lavage fluid (BALF) and lung CFU values were determined. PAFR protein levels were assessed by using immunofluorescence and immunohistochemistry, and PAFR mRNA expression was assessed by using quantitative PCR. PAFR was blocked by CV-3988, and oxidative stress was attenuated by N-acetylcysteine. Results: MS-WF exhibited high oxidative potential. In A549 and BEAS-2B cells MS-WF increased pneumococcal adhesion and infection and PAFR protein expression. Both CV-3988 and N-acetylcysteine reduced MS-WF–stimulated pneumococcal adhesion and infection of airway cells. MS-WF increased mouse lung PAFR mRNA expression and increased BALF and lung pneumococcal CFU values. In MS-WF–exposed mice CV-3988 reduced BALF CFU values. Hypersusceptibility of welders to pneumococcal pneumonia is in part mediated by the capacity of welding fumes to increase PAFR-dependent pneumococcal adhesion and infection of lower airway cells.