Goldblum S E, Sun W L
Department of Medicine, Veterans Administration Medical Center, University of Maryland School of Medicine, Baltimore 21201.
Am J Physiol. 1990 Feb;258(2 Pt 1):L57-67. doi: 10.1152/ajplung.1990.258.2.L57.
Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator of pulmonary vascular endothelial injury. We studied the effect of human recombinant TNF alpha (rTNF alpha) on transfer of 14C-labeled bovine serum albumin (BSA) across cultured bovine pulmonary arterial endothelial cell monolayers. rTNF alpha induced a dose-, time-, and temperature-dependent increment in transendothelial [14C]BSA flux. Only after an incubation time of greater than or equal to 4 h did rTNF alpha significantly (P less than 0.005) increase transendothelial albumin flux. rTNF alpha exposure times as brief as 5 min induced significantly (P less than 0.005) increased albumin transfer at 6 h. Although this initial rTNF alpha-endothelial interaction was not temperature dependent, the subsequent barrier dysfunction could only be generated at 37 degrees C. The rTNF alpha-induced changes could not be ascribed to endothelial cell cytotoxicity and was not blocked by protein synthesis inhibition. The effects of rTNF alpha on endothelial permeability were reversible and not specific for albumin transfer. Therefore, rTNF alpha may influence the movement of macromolecules across the pulmonary vascular endothelial barrier.
肿瘤坏死因子-α（TNFα）被认为是肺血管内皮损伤的介质。我们研究了重组人TNFα（rTNFα）对14C标记的牛血清白蛋白（BSA）跨培养的牛肺动脉内皮细胞单层转运的影响。rTNFα诱导跨内皮[14C]BSA通量呈剂量、时间和温度依赖性增加。只有在孵育时间大于或等于4小时后，rTNFα才显著（P<0.005）增加跨内皮白蛋白通量。rTNFα暴露时间短至5分钟在6小时时显著（P<0.005）增加白蛋白转运。虽然这种最初的rTNFα-内皮相互作用不依赖温度，但随后的屏障功能障碍仅在37℃时产生。rTNFα诱导的变化不能归因于内皮细胞毒性，也不受蛋白质合成抑制的阻断。rTNFα对内皮通透性的影响是可逆的，且对白蛋白转运不具有特异性。因此，rTNFα可能影响大分子跨肺血管内皮屏障的移动。
