TUMOR NECROSIS FACTOR ALPHA-INDUCED PULMONARY VASCULAR ENDOTHELIAL INJURY
TUMOR NECROSIS FACTOR ALPHA-INDUCED PULMONARY VASCULAR ENDOTHELIAL INJURY
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DOI：
10.1128/iai.57.4.1218-1226.1989
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发表时间：
1989-04-01
影响因子：
3.1
通讯作者：
MCCLAIN, CJ
中科院分区：
文献类型：
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作者：
GOLDBLUM, SE;HENNIG, B;MCCLAIN, CJ
肿瘤坏死因子α（TNF-α）介导急性期反应的组分，刺激粒细胞代谢，并诱导内皮细胞表面变化。我们研究了人重组TNF-α。（rTNF-α）增加肺水肿形成和肺血管通透性。向预先输注125 I-白蛋白的兔施用rTNF-α。或盐水。处死动物，测定肺湿/干重比以及支气管肺泡灌洗液和血浆125 I活性。rTNF-.alpha.与生理盐水对照组相比，肺湿/干重比增加151%（P < 0.02），支气管肺泡灌洗液/血浆125 I活性比增加376%（P < 0.01）。肺切片的电子显微镜检查显示内皮损伤、血管周围水肿和超微结构渗透性示踪剂外渗。为了证明rTNF-α。可直接增加体外培养的肺血管内皮细胞的通透性，我们研究了白蛋白跨培养的猪肺动脉内皮细胞单层的转移。rTNF-.alpha.在不存在粒细胞效应细胞的情况下，诱导跨内皮白蛋白通量的时间依赖性剂量反应性增量。这些观察结果表明，rTNF-α。可在体内和体外引起急性肺血管内皮损伤。
Tumor necrosis factor .alpha. (TNF-.alpha.) mediates components of the acute-phase response, stimulates granulocyte metabolism, and induces endothelial cell surfaces changes. We studied whether human recombinant TNF-.alpha. (rTNF-.alpha.) could increase pulmonary edema formation and pulmonary vascular permeability. Rabbits preinfused with 125I-albumin were administered rTNF-.alpha. or saline. Animals were sacrificed, and lung wet/dry weights ratios as well as bronchoalveolar lavage fluid and plasma 125I activities were determined. rTNF-.alpha. increased lung wet/dry weight ratios by 151% (P < 0.02) and bronchoalveolar lavage fluid/plasma 125I activity ratios by 376% (P < 0.01) compared with values for saline controls. Electron microscopy of lung sections demonstrated endothelial injury, perivascular edema, and extravasation of a ultrastructural permeability tracer. To demonstrate that rTNF-.alpha. could directly increase pulmonary vascular endothelial permeability in vitro, we studied albumin transfer across cultured porcine pulmonary artery endothelial cell monolayers. rTNF-.alpha. induced time-dependent dose-response increments in transendothelial albumin flux in the absence of granulocyte effector cells. These observations suggest that rTNF-.alpha. can provoke acute pulmonary vascular endothelial injury in vivo as well as in vitro.