Corne J, Chupp G, Lee C G, Homer R J, Zhu Z, Chen Q, Ma B, Du Y, Roux F, McArdle J, Waxman A B, Elias J A
Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
J Clin Invest. 2000 Sep;106(6):783-91. doi: 10.1172/JCI9674.
Hyperoxia is an important cause of acute lung injury. To determine whether IL-13 is protective in hyperoxia, we compared the survival in 100% O(2) of transgenic mice that overexpress IL-13 in the lung and of nontransgenic littermate controls. IL-13 enhanced survival in 100% O(2). One hundred percent of nontransgenic mice died in 4-5 days, whereas 100% of IL-13-overexpressing mice lived for more than 7 days, and many lived 10-14 days. IL-13 also stimulated VEGF accumulation in mice breathing room air, and it interacted with 100% (2) to increase VEGF accumulation further. The 164-amino acid isoform was the major VEGF moiety in bronchoalveolar lavage from transgenic mice in room air, whereas the 120- and 188-amino acid isoforms accumulated in these mice during hyperoxia. In addition, antibody neutralization of VEGF decreased the survival of IL-13-overexpressing mice in 100% (2). These studies demonstrate that IL-13 has protective effects in hyperoxic acute lung injury. They also demonstrate that IL-13, alone and in combination with 100% (2), stimulates pulmonary VEGF accumulation, that this stimulation is isoform-specific, and that the protective effects of IL-13 are mediated, in part, by VEGF.
高氧是急性肺损伤的一个重要原因。为了确定白细胞介素-13（IL-13）在高氧环境中是否具有保护作用，我们比较了肺中过度表达IL-13的转基因小鼠和同窝非转基因对照小鼠在100%氧气环境中的存活率。IL-13提高了在100%氧气环境中的存活率。100%的非转基因小鼠在4 - 5天内死亡，而100%的IL-13过度表达小鼠存活超过7天，许多存活10 - 14天。IL-13还刺激了呼吸室内空气的小鼠体内血管内皮生长因子（VEGF）的积累，并且它与100%氧气共同作用进一步增加VEGF的积累。164个氨基酸的异构体是在室内空气中转基因小鼠支气管肺泡灌洗中主要的VEGF部分，而120和188个氨基酸的异构体在高氧期间在这些小鼠中积累。此外，VEGF的抗体中和降低了IL-13过度表达小鼠在100%氧气环境中的存活率。这些研究表明IL-13在高氧急性肺损伤中具有保护作用。它们还表明，IL-13单独以及与100%氧气联合作用时，刺激肺VEGF的积累，这种刺激是异构体特异性的，并且IL-13的保护作用部分是由VEGF介导的。
