Taraseviciene-Stewart Laima, Douglas Ivor S, Nana-Sinkam Patrick S, Lee Jong D, Tuder Rubin M, Nicolls Mark R, Voelkel Norbert F
University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
Proc Am Thorac Soc. 2006 Nov;3(8):687-90. doi: 10.1513/pats.200605-105SF.
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.
在终末期慢性阻塞性肺疾病（COPD）患者中，导致气腔扩大的肺泡破坏通常呈进行性发展，即便戒烟后也是如此。多个实验室已积累数据，证明在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，有报道称重度COPD患者的肺实质中存在T淋巴细胞和B淋巴细胞聚集，且常形成滤泡。此外，有人推测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细胞克隆的概念相符。在此背景下，我们建立了成年大鼠自身免疫性肺气肿模型。基于已发表的数据表明用人脐静脉内皮细胞（HUVECs）免疫小鼠会产生抗血管内皮生长因子（VEGF）受体II（KDR）抗体，以及我们自己的数据显示在成年大鼠中给予VEGF受体阻滞剂会导致肺气肿，我们推断在大鼠腹腔内注射HUVECs会同时产生抗VEGF受体抗体和肺气肿。事实上，腹腔内注射HUVECs导致了肺气肿。我们进一步探究了该模型的自身免疫性质，在经HUVEC免疫的大鼠血清中鉴定出KDR抗体，并将肺气肿大鼠的血清注射到未接触过的大鼠和小鼠体内，结果导致了肺气肿。目前，我们正在研究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鉴定出了抗内皮细胞抗体。
