Powers Kinga A, Kapus Andras, Khadaroo Rachel G, Papia Giuseppe, Rotstein Ori D
Department of Surgery, University of Toronto, University Health Network, Toronto General Hospital, Ontario, Canada.
Surgery. 2002 Aug;132(2):391-8. doi: 10.1067/msy.2002.126508.
Polymorphonuclear neutrophil (PMN) sequestration in the lung is a hallmark of acute respiratory distress syndrome (ARDS). We have shown that 25% Albumin (A25) resuscitation attenuates lung injury after hemorrhagic shock and lipopolysaccharide (LPS) exposure by reducing lung leukosequestration. We hypothesize that this protective property is mediated by alteration of neutrophil-endothelial cell adhesive interactions.
A 2-hit rodent model of shock resuscitation was used. CD11b and L-selectin were measured using flow cytometry in rat and human neutrophils ex vivo. Intercellular adhesion molecule-1 (ICAM-1) levels were measured by Northern blot and immunohistochemistry.
Resuscitation with A25 attenuated the increase in PMN CD11b expression in Ringer's lactate (RL) resuscitated animals at end resuscitation and at 4-hour post-LPS. While PMN L-selectin levels remained stable in RL treated animals, A25 resuscitation resulted in a significant decrease in surface L-selectin expression at 4-hour post-LPS. ICAM-1 lung endothelial cell mRNA, was increased in RL resuscitated animals, however reduced with A25 use by 51%. The LPS induced ICAM-1 endothelial cell protein expression was also prevented with A25 resuscitation. Antioxidant property of albumin was shown to play a critical role in altering CD11b expression.
The A25 exerts its lung-protective activity at various levels including altering the interaction between neutrophils and endothelial cells via suppressed expression of adhesion molecules. These findings suggest a novel role for A25 as an anti-inflammatory agent in PMN-mediated diseases such as ARDS.
多形核中性粒细胞（PMN）在肺内的滞留是急性呼吸窘迫综合征（ARDS）的一个标志。我们已经表明，25%白蛋白（A25）复苏通过减少肺白细胞滞留减轻失血性休克和脂多糖（LPS）暴露后的肺损伤。我们假设这种保护特性是由中性粒细胞与内皮细胞粘附相互作用的改变介导的。
使用双打击啮齿动物休克复苏模型。通过体外流式细胞术测量大鼠和人中性粒细胞中的CD11b和L-选择素。通过Northern印迹和免疫组织化学测量细胞间粘附分子-1（ICAM-1）水平。
在复苏结束时和LPS处理后4小时，A25复苏减弱了乳酸林格液（RL）复苏动物中PMN CD11b表达的增加。虽然在RL处理的动物中PMN L-选择素水平保持稳定，但A25复苏导致LPS处理后4小时表面L-选择素表达显著降低。RL复苏动物中ICAM-1肺内皮细胞mRNA增加，但使用A25后降低了51%。A25复苏也阻止了LPS诱导的ICAM-1内皮细胞蛋白表达。白蛋白的抗氧化特性在改变CD11b表达中起关键作用。
A25在多个水平发挥其肺保护活性，包括通过抑制粘附分子表达改变中性粒细胞与内皮细胞之间的相互作用。这些发现表明A25作为一种抗炎剂在PMN介导的疾病如ARDS中具有新的作用。
