Tzortzaki E G, Siafakas N M
Department of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion 71110, Greece.
Eur Respir J. 2009 Aug;34(2):310-5. doi: 10.1183/09031936.00067008.
Chronic obstructive pulmonary disease (COPD) is generally thought to depend on an aberrant immune response to a noxious or infectious agent, which may cause chronic inflammation. However, the initiation of this abnormal response is not fully understood. Here, we propose a new hypothesis for the beginning of COPD, that the immune response to inhaled agents, mainly cigarette smoke, is directed toward the airway epithelium, due to oxidative DNA damage of the lung epithelial barrier cells (LEBCs). The steps of this model are as follows. 1) Cigarette smoke induces oxidative DNA damage of LEBCs. 2) The acquired mutations are expressed at the microsatellite DNA level of LEBCs. 3) The altered LEBCs are recognised by dendritic cells (DCs) as "nonself". DCs travel, with the new information, to the lymph nodes, presenting it to the naïve T-lymphocytes. 4) A predominant CD8+ cytotoxic T-lymphocyte proliferation occurs. The CD8+ cells, by releasing perforin and granzymes, attack the altered LEBCs activating cell death cascades. Obviously, the above scenario needs further experimental exploration. However, it is an attractive model for the initiation of the abnormal inflammation in COPD, comprising oxidative DNA damage of LEBCs and host immune response.
慢性阻塞性肺疾病（COPD）通常被认为取决于对有害或感染性因子的异常免疫反应，这可能会导致慢性炎症。然而，这种异常反应的起始机制尚未完全明确。在此，我们提出一种关于COPD起始的新假说，即由于肺上皮屏障细胞（LEBCs）的氧化性DNA损伤，对吸入性因子（主要是香烟烟雾）的免疫反应是针对气道上皮的。该模型的步骤如下：1）香烟烟雾诱导LEBCs的氧化性DNA损伤。2）获得性突变在LEBCs的微卫星DNA水平表达。3）改变后的LEBCs被树突状细胞（DCs）识别为“非自身”。DCs携带新信息前往淋巴结，将其呈递给幼稚T淋巴细胞。4）发生主要的CD8 + 细胞毒性T淋巴细胞增殖。CD8 + 细胞通过释放穿孔素和颗粒酶攻击改变后的LEBCs，激活细胞死亡级联反应。显然，上述设想需要进一步的实验探索。然而，它是一个关于COPD异常炎症起始的有吸引力的模型，包括LEBCs的氧化性DNA损伤和宿主免疫反应。
