NEUTROPHIL-DEPENDENT, OXYGEN-RADICAL MEDIATED LUNG INJURY ASSOCIATED WITH ACUTE-PANCREATITIS
NEUTROPHIL-DEPENDENT, OXYGEN-RADICAL MEDIATED LUNG INJURY ASSOCIATED WITH ACUTE-PANCREATITIS
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DOI：
10.1097/00000658-198912000-00008
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发表时间：
1989-12-01
影响因子：
9
通讯作者：
WARD, PA
中科院分区：
文献类型：
--
作者：
GUICE, KS;OLDHAM, KT;WARD, PA
蛙皮素诱导的大鼠急性胰腺炎与可逆性肺损伤相关，其特征在于肺泡毛细血管内皮细胞损伤、微血管通透性增加、间质水肿形成以及肺泡内出血和纤维蛋白沉积。介质在这种损伤中的作用进行了分析，使用重量数据，微血管通透性指数，电子显微镜，和定量形态分析。特异性抗体诱导的中性粒细胞耗竭对肺损伤具有高度保护作用。阻断补体途径（使用低剂量眼镜蛇毒因子）也可保护肺免受损伤。过氧化氢酶和超氧化物歧化酶也具有保护作用。铁螯合剂去铁胺和羟自由基清除剂二甲基亚砜对急性肺损伤没有保护作用。这些数据表明，补体、中性粒细胞和中性粒细胞来源的（H2 O2依赖性）氧产物介导了蓝蛋白诱导的胰腺炎继发性肺损伤。与其他嗜铁蛋白依赖性、氧自由基介导的肺损伤模型相反，这种肺损伤似乎不是铁依赖性和羟基自由基介导的损伤。我们推测，急性胰腺炎的过程导致补体激活，随后中性粒细胞募集，隔离，并粘附到肺泡毛细血管内皮细胞。最终，肺损伤似乎是由于局部内皮细胞损伤继发于嗜中性粒细胞产生的氧产物，可能是髓过氧化物酶依赖性的。图像
Cerulein-induced acute pancreatitis in rats is associated with a reversible lung injury that is characterized by alveolar capillary endothelial-cell injury, increased microvascular permeability, interstitial edema formation, and intraalveolar hemorrhage and fibrin deposition. The role of mediators in this injury was analyzed using gravimetric data, microvascular permeability indices, electron microscopy, and a quantitative morphometric analysis. Neutrophil depletion induced by a specific antibody was highly protective against lung injury. Interruption of the complement pathway (using low dose Naja naja cobra venom factor) also protected against lung injury. Catalase and superoxide dismutase were also protective. The iron chelator deferoxamine and the hydroxyl radical scavenger, dimethylsulfoxide, were not protective against acute lung injury. These data suggest that complement, neutrophils, and neutrophil-derived (H2O2-dependent) oxygen products mediate lung injury that occurs secondary to cerulein-induced pancreatitis. In contrast to other models of neutrophil-dependent, oxygen-radical-mediated lung injury, this lung injury does not appear to be an iron-dependent and hydroxyl-radical mediated injury. We postulate that the process of acute pancreatitis leads to complement activation followed by neutrophil recruitment, sequestration, and adherence to alveolar capillary endothelial cells. Ultimately lung injury appears to result from local endothelial-cell injury secondary to neutrophil-generated oxygen products that may be myeloperoxidase dependent. Images