Carden D, Xiao F, Moak C, Willis B H, Robinson-Jackson S, Alexander S
Department of Medicine, Louisiana State University Medical Center, Shreveport, Louisiana 71130, USA.
Am J Physiol. 1998 Aug;275(2):H385-92. doi: 10.1152/ajpheart.1998.275.2.H385.
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.
肠道缺血再灌注（I-R）与肺损伤及急性呼吸窘迫综合征相关。本研究的假设是肠道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。用肠道I-R后获得的血液或血浆灌注离体大鼠肺，测量肺中性粒细胞滞留、损伤情况及支气管肺泡灌洗（BAL）弹性蛋白酶水平。用I-R血液灌注导致肺中性粒细胞积聚、损伤，并使BAL弹性蛋白酶增加。弹性蛋白酶抑制剂L-658758可减轻这些效应。在肠道再灌注前干扰中性粒细胞黏附可阻止BAL弹性蛋白酶积聚。还评估了内皮连接蛋白（钙黏蛋白）在I-R引发的肺损伤中的作用。活化的人中性粒细胞可水解人脐静脉内皮细胞中的钙黏蛋白。此外，急性呼吸窘迫综合征患者的血浆中含有可溶性钙黏蛋白片段。本研究结果表明，全身活化的中性粒细胞释放的弹性蛋白酶有助于肺中性粒细胞积聚和肺微血管损伤。弹性蛋白酶介导的内皮细胞钙黏蛋白蛋白水解可能是肠道I-R后肺微血管完整性被破坏的机制。
