Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital; Eberhard-Karls University, Tübingen, Germany.
Department of Anesthesiology and Perioperative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Mucosal Immunol. 2014 Jul;7(4):879-91. doi: 10.1038/mi.2013.104. Epub 2013 Dec 18.
Acute pulmonary inflammation during lung injury is initiated by the migration of neutrophils into the alveolar space. The severity of these inflammatory changes within the pulmonary tissue determines the severity of lung injury and ultimately patient outcome. Recent work has demonstrated that the guidance protein Semaphorin 7A propagates the infiltration of neutrophils into an hypoxic tissue site, yet the role of its target receptor Plexin C1 (PLXNC1) during lung injury is to date unknown. We demonstrate here that PLXNC1(+) neutrophils are present within the alveolar space and that PLXNC1 is induced in vitro and in vivo during lung injury. In a model of high-pressure ventilation PLXNC1(-/-) animals show decreased signs of alveolar inflammation and improved survival compared with wild-type controls. Studies employing chimeric animals identified the hematopoietic expression of PLXNC1 to be of crucial importance for the observed results. Functional inhibition of PLXNC1 resulted in improved survival and ameliorated the signs of inflammation within the lung. Furthermore, the injection of a peptide binding to PLXNC1 resulted in improved survival and attenuated pulmonary inflammation. As such we demonstrate here, that previously unknown PLXNC1 holds significant importance for degree of pulmonary inflammation and determines outcome during experimental lung injury.
在肺损伤期间，急性肺炎症是由中性粒细胞迁移到肺泡空间引发的。肺部组织中这些炎症变化的严重程度决定了肺损伤的严重程度，并最终影响患者的预后。最近的研究表明，导向蛋白 Semaforin 7A 促使中性粒细胞浸润到缺氧组织部位，但迄今为止，其靶受体 Plexin C1 (PLXNC1) 在肺损伤中的作用尚不清楚。我们在这里证明，PLXNC1(+)中性粒细胞存在于肺泡空间中，并且在体外和体内肺损伤过程中诱导表达 PLXNC1。在高压通气模型中，PLXNC1(-/-)动物表现出肺泡炎症的迹象减少，与野生型对照相比，存活率提高。采用嵌合动物的研究表明，PLXNC1 的造血表达对观察到的结果至关重要。PLXNC1 的功能抑制导致存活率提高，并改善肺部炎症的迹象。此外，注射与 PLXNC1 结合的肽导致存活率提高，并减轻肺部炎症。因此，我们在这里证明，以前未知的 PLXNC1 对肺炎症的严重程度具有重要意义，并决定实验性肺损伤期间的结果。
