GRANULOCYTE DEPLETION PREVENTS TUMOR NECROSIS FACTOR-MEDIATED ACUTE LUNG INJURY IN GUINEA-PIGS
GRANULOCYTE DEPLETION PREVENTS TUMOR NECROSIS FACTOR-MEDIATED ACUTE LUNG INJURY IN GUINEA-PIGS
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DOI：
10.1164/ajrccm/138.5.1300
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发表时间：
1988-11-01
期刊：
影响因子：
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通讯作者：
RAFFIN, TA
中科院分区：
文献类型：
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作者：
STEPHENS, KE;ISHIZAKA, A;RAFFIN, TA
研究多形核中性粒细胞（PMN）和其它粒细胞在由肿瘤坏死因子α引起的急性肺损伤的发病机制中的作用。(TNF)我们比较了正常（粒细胞充足）豚鼠和TNF治疗的粒细胞减少豚鼠的通透性水肿和肺组织病理学。用环磷酰胺耗竭循环粒细胞。两组正常动物用盐水（PMN+/对照）或1.4 × 10 - 6处理。106 U/kg重组人TNF（PMN+/TNF）。三个粒细胞减少组用盐水（PMN-/对照）、TNF（PMN-/TNF）或静脉内输注2 × 10 - 6 μ g/ml的TNF处理。109大肠杆菌菌株J 96（PMN-/败血症）。我们测量了支气管肺泡灌洗液（BAL）和全肺组织中125 I标记的白蛋白的量以及肺湿/干重比，以评估肺经血管蛋白通量和水肿。我们还定量了BAL液和固定肺组织中的PMN。PMN+/对照组、PMN-/对照组或PMN-/TNF组之间的任何这些参数均无统计学显著差异，但PMN+/对照组的PMN/肺泡比PMN-组多。然而，与所有其他组相比，PMN+/TNF和PMN-/脓毒症组的BAL液和肺组织中125 I标记的白蛋白的量增加（p < 0.01），湿/干肺重量比增加（p < 0.05）。组织学上，PMN+/TNF组可见毛细血管充血和中度炎症，PMN-/脓毒症组可见急性炎症和肉眼肺泡出血。从这些数据，并通过与以前的研究PMN+/脓毒症动物的比较，我们得出结论，粒细胞耗竭与环磷酰胺保护TNF-介导的，但不是脓毒症，急性肺损伤在这个模型中。
To examine the role of polymorphonuclear neutrophils (PMN) and other granulocytes in the pathogenesis of acute lung injury caused by tumor necrosis factor .alpha. (TNF), we compared the permeability edema and pulmonary histopathology in normal (granulocyte sufficient) guinea pigs and in granulocytopenic guinea pigs treated with TNF. Circulating granulocytes were depleted with cyclophosphamide. Two groups of normal animals were treated with either saline (PMN+/Control) or 1.4 .times. 106 U/kg recombinant human TNF (PMN+/TNF). Three granulocytopenic groups were treated with either saline (PMN-/Control), TNF (PMN-/TNF), or intravenous infusion of 2 .times. 109 Escherichia coli strain J96 (PMN-/Sepsis). We measured the amount of 125I-labeled albumin in bronchoalveolar lavage (BAL) fluid and whole lung tissue and the wet/dry lung weight ratio to assess pulmonary transvascular protein flux and edema. We also quantified PMN in BAL fluid and fixed lung tissue. There were no statistically significant differences in any of these parameters between the PMN+/Control, PMN-/Control, or PMN-/TNF groups, except that the PMN+/Control predictably had more PMN/alveolus than the PMN- groups. However, both the PMN+/TNF and the PMN-/Sepsis groups had increased amounts of 125I-labeled albumin in BAL fluid and lung tissue (p < 0.01) and increased wet/dry lung weight ratios (p < 0.05), compared to all other groups. Histopathologically, capillary congestion and moderate inflammation were seen in the PMN+/TNF group, and acute inflammation and gross alveolar hemorrhage were seen in the PMN-/Sepsis group. From these data, and by comparison with previous studies of PMN+/Sepsis animals, we conclude that granulocyte depletion with cyclophosphamide protects against TNF-mediated, but not septic, acute lung injury in this model.