Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins
Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins
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DOI：
10.1152/ajpheart.1998.275.2.h385
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发表时间：
1998-08-01
影响因子：
4.8
通讯作者：
Alexander, S
中科院分区：
文献类型：
--
作者：
Carden, D;Xiao, F;Alexander, S
肠缺血再灌注(I-R)与肺损伤和急性呼吸窘迫综合征有关。这项研究的假设是肠I-R激活循环中的中性粒细胞，以促进弹性蛋白酶介导的肺损伤。用肠I-R后取血或血浆灌流大鼠离体肺，测定中性粒细胞滞留、肺损伤和支气管肺泡灌洗(BAL)弹性蛋白酶。I-R血灌流可引起肺组织中性粒细胞聚集和损伤，并使BAL弹性蛋白酶升高。这些作用可被弹性蛋白酶抑制剂L-658758减弱。干预肠再灌流前中性粒细胞黏附可阻断BAL弹性蛋白酶的积聚。血管内皮细胞连接蛋白(钙粘附素)在I-R诱导的肺损伤中的作用也被评估。活化的人中性粒细胞蛋白水解人脐静脉内皮细胞中的钙粘附素。此外，急性呼吸窘迫综合征患者的血浆中含有可溶性钙粘附素片段。本研究结果提示，系统激活的中性粒细胞释放的弹性蛋白酶参与了肺中性粒细胞聚集和肺微血管损伤。弹性酶介导的内皮细胞钙粘附素蛋白分解可能是肠I-R后肺微血管完整性被破坏的机制之一。
Intestinal ischemia-reperfusion (I-R) is associated with lung injury and the acute respiratory distress syndrome. The hypothesis of this study was that intestinal I-R activates circulating neutrophils to promote elastase-mediated lung injury. Isolated rat lungs were perfused with blood or plasma obtained after intestinal I-R, and lung neutrophil retention and injury and bronchoalveolar lavage (BAL) elastase were measured. Perfusion with I-R blood caused lung neutrophil accumulation and injury and increased BAL elastase. These effects were attenuated by the elastase inhibitor L-658758. Interference with neutrophil adherence before gut reperfusion blocked BAL elastase accumulation. The role of endothelial junction proteins (cadherins) in I-R-elicited lung damage was also evaluated. Activated human neutrophils proteolyzed cadherins in human umbilical vein endothelial cells. Furthermore, plasma of patients with acute respiratory distress syndrome contained soluble cadherin fragments. The results of this study suggest that the elastase released by systemically activated neutrophils contributes to lung neutrophil accumulation and pulmonary microvascular injury. Elastase-mediated proteolysis of endothelial cell cadherins may represent the mechanism through which lung microvascular integrity is disrupted after intestinal I-R.