Emphysema: an autoimmune vascular disease?
Emphysema: an autoimmune vascular disease?
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DOI：
10.1513/pats.200405-033ms
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Taraseviciene-Stewart, Laima
中科院分区：
文献类型：
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作者：
Voelkel, Norbert;Taraseviciene-Stewart, Laima
我们认为，一个内源性的维护程序控制肺细胞周转，细胞凋亡和组织修复，肺气肿是肺结构维护程序崩溃的表现。肺气肿可以通过以下三种方法在大鼠中实验性诱导：使用SU 5416（一种小分子酪氨酸激酶抑制剂）阻断血管内皮生长因子受体;甲基强的松龙，其激活基质金属蛋白酶-9并降低Akt磷酸化;以及针对内皮细胞的抗体（自身免疫性肺气肿）。SU 5416诱导的肺气肿与细胞色素P450和氧化应激的肺诱导有关，超氧化物歧化酶模拟物或N-乙酰半胱氨酸可预防这种形式的肺气肿。广谱金属蛋白酶抑制剂可预防甲基强的松龙诱导的肺气肿，最后，自身免疫性肺气肿与肺组织金属蛋白酶-9表达增加和肺泡间隔细胞凋亡相关。缺乏CD 4 + T细胞的无胸腺大鼠可防止自身免疫性肺气肿，而CD 4 + T细胞的过继转移可导致幼稚成年大鼠的自身免疫性肺气肿。似乎血管内皮生长因子及其受体的信号传导在肺结构维持程序中起着核心作用，并且氧化应激、蛋白水解和细胞凋亡可能在肺细胞破坏的时刻同时发生。有趣的是，甲基强的松龙模型说明炎症不是肺气肿发展所必需的。
We propose that an endogenous maintenance program controls lung cell turnover, apoptosis, and tissue repair, and that emphysema is a manifestation of the breakdown of the lung structure maintenance program. Emphysema can be induced experimentally in rats by three methods: blockade of vascular endothelial growth factor receptors using SU5416, a small molecule-tyrosine kinase inhibitor; methylprednisolone, which activates matrix metalloproteinase-9 and decreases Akt phosphorylation; and antibodies directed against endothelial cells (autoimmune emphysema). SU5416-induced emphysema is associated with lung induction of cytochrome P450 and oxidant stress, and a superoxide dismutase mimetic or N-acetylcysteine prevents this form of emphysema. A broad-spectrum metalloproteinase inhibitor prevents methylprednisolone-induced emphysema and, finally, autoimmune emphysema is associated with increased lung tissue metalloproteinase-9 expression and alveolar septal cell apoptosis. Athymic rats, which lack CD4+ T cells, are protected against autoimmune emphysema, whereas adoptive transfer of CD4+ T cells causes autoimmune emphysema in naive adult rats. It appears that vascular endothelial growth factor and signaling via its receptors plays a central role in the lung structural maintenance program, and oxidative stress, proteolysis, and apoptosis may coincide in the moment of lung cell destruction. Interestingly, the methylprednisolone model illustrates that inflammation is not necessary for the development of emphysema.