Is alveolar destruction and emphysema in chronic obstructive pulmonary disease an immune disease?
Is alveolar destruction and emphysema in chronic obstructive pulmonary disease an immune disease?
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DOI：
10.1513/pats.200605-105sf
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发表时间：
2006-11-01
期刊：
影响因子：
--
通讯作者：
Voelkel, Norbert F
中科院分区：
文献类型：
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作者：
Taraseviciene-Stewart, Laima;Douglas, Ivor S;Voelkel, Norbert F
终末期慢性阻塞性肺疾病（COPD）患者的肺泡破坏导致气道扩大，尽管戒烟，但通常是进行性的。几个实验室已经积累了数据，证明COPD患者的支气管活检标本和肺组织切片中存在免疫细胞。最近，有报道称，严重COPD患者的肺实质中存在T和B淋巴细胞的积聚，通常形成滤泡。此外，据推测，COPD可能存在自身免疫成分。T细胞受体分析提供的数据与COPD患者肺组织中T细胞克隆的概念一致。在此背景下，我们在成年大鼠中建立了自身免疫性肺气肿模型。基于已发表的数据显示，用人脐静脉内皮细胞（HUVEC）免疫小鼠会导致抗血管内皮生长因子（VEGF）受体II（KDR）抗体的产生，以及我们自己的数据表明，在成年大鼠中给予VEGF受体阻滞剂会导致肺气肿，我们推断，大鼠腹腔内注射HUVEC会产生抗VEGF受体抗体和肺气肿。事实上，腹膜内注射HUVEC引起肺气肿。我们进一步探索了该模型的自身免疫性质，鉴定了HUVEC免疫大鼠血清中的KDR抗体，并将来自肺气肿大鼠的血清注射到幼稚大鼠和小鼠中，导致肺气肿。目前，我们正在调查香烟烟雾提取物是否会导致肺气肿。我们最近在终末期肺气肿患者的血清中发现了抗内皮细胞抗体。
The alveolar destruction leading to airspace enlargement in patients with end-stage chronic obstructive pulmonary disease (COPD) is frequently progressive, despite smoking cessation. Several laboratories have accumulated data demonstrating the presence of immune cells in bronchial biopsy specimens and lung tissue sections from patients with COPD. Recently, the accumulation of T and B lymphocytes, often forming follicles, in the lung parenchyma from patients with severe COPD has been reported. In addition, it has been postulated that there might be an autoimmune component to COPD. T-cell receptor analysis has provided data consistent with the concept of T-cell clones in the lung tissue from patients with COPD. Against this background, we developed a model of autoimmune emphysema in adult rats. Based on published data showing that immunization of mice with human umbilical vein endothelial cells (HUVECs) causes production of anti-vascular endothelial growth factor (VEGF) receptor II (KDR) antibodies, and our own data indicating that administration of a VEGF receptor blocker in adult rats causes emphysema, we reasoned that intraperitoneal injection of HUVECs in rats would generate both anti-VEGF receptor antibodies and emphysema. Indeed, intraperitoneal injection of HUVECs caused emphysema. We further explored the autoimmune nature of this model, identified KDR antibodies in the serum of HUVEC-immunized rats, and injected serum from the emphysematous rats into naive rats and mice, which resulted in emphysema. Presently, we are in the process of investigating whether cigarette smoke extract causes emphysema. We recently identified anti-endothelial cell antibodies in the serum of patients with end-stage emphysema.