Paulsson Magnus, Che Karlhans F, Ahl Jonas, Tham Johan, Sandblad Linda, Smith Margaretha E, Qvarfordt Ingemar, Su Yu-Ching, Lindén Anders, Riesbeck Kristian
Clinical Microbiology, Department of Translational Medicine, Faculty of Medicine, Lund University, Lund, Sweden.
Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Front Microbiol. 2018 Jul 13;9:1559. doi: 10.3389/fmicb.2018.01559. eCollection 2018.
Pathogens causing pneumonia utilize the complement regulator vitronectin to evade complement-mediated killing. Although vitronectin is associated with several chronic lung diseases, the role of bronchoalveolar vitronectin in pneumonia has not been studied. This study sought to reveal the involvement of vitronectin in the bronchoalveolar space during pneumonia, to assess the effect of outer membrane vesicles and endotoxin on vitronectin release, and to determine whether bacterial pathogens utilize pulmonary vitronectin for evasion. Vitronectin was analyzed in cell-free bronchoalveolar lavage fluid harvested from patients with pneumonia ( = 8) and from healthy volunteers after subsegmental endotoxin instillation ( = 13). Vitronectin binding by and was analyzed, and subsequent complement evasion was assessed by serum challenge. The effects of outer membrane vesicles on vitronectin production in mouse lungs and human type II alveolar epithelial cells (A549) were determined. We detected increased vitronectin concentrations in lavage fluid during pneumonia ( 0.0063) and after bronchial endotoxin challenge ( 0.016). The capture of vitronectin by bacteria significantly reduced complement-mediated lysis. Following challenge with vesicles, vitronectin was detected in mouse bronchoalveolar space, and mouse alveolar epithelial cells as well as A549 cells contained increased levels of vitronectin. Taken together, outer membrane vesicles and endotoxin from Gram-negative bacteria induce vitronectin, which is released into the bronchoalveolar space, and used for evasion of complement-mediated clearance.
引起肺炎的病原体利用补体调节蛋白玻连蛋白来逃避补体介导的杀伤作用。尽管玻连蛋白与多种慢性肺部疾病有关，但支气管肺泡玻连蛋白在肺炎中的作用尚未得到研究。本研究旨在揭示玻连蛋白在肺炎期间支气管肺泡空间中的作用，评估外膜囊泡和内毒素对玻连蛋白释放的影响，并确定细菌病原体是否利用肺部玻连蛋白进行逃避。对从肺炎患者（n = 8）和亚节段内毒素注入后的健康志愿者（n = 13）采集的无细胞支气管肺泡灌洗液中的玻连蛋白进行了分析。分析了肺炎链球菌和大肠杆菌与玻连蛋白的结合情况，并通过血清攻击评估随后的补体逃避情况。确定了外膜囊泡对小鼠肺部和人II型肺泡上皮细胞（A549）中玻连蛋白产生的影响。我们检测到肺炎期间灌洗液中玻连蛋白浓度升高（P < 0.0063），支气管内毒素攻击后也升高（P < 0.016）。细菌对玻连蛋白的捕获显著降低了补体介导的裂解作用。用囊泡攻击后，在小鼠支气管肺泡空间中检测到玻连蛋白，并且小鼠肺泡上皮细胞以及A549细胞中玻连蛋白水平升高。综上所述，革兰氏阴性菌的外膜囊泡和内毒素诱导玻连蛋白，其释放到支气管肺泡空间中，并用于逃避补体介导的清除。
