The role of reactive oxygen and nitrogen species in the response of airway epithelium to particulates.
The role of reactive oxygen and nitrogen species in the response of airway epithelium to particulates.
复制标题
活性氧和氮种在气道上皮对颗粒的反应中的作用。
DOI：
10.1289/ehp.97105s51301
复制
发表时间：
1997-09
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
--
作者：
流行病学和职业研究表明，由于吸入颗粒空气污染物，对健康产生不利影响，但确切的生物学机制尚未完全建立。气管支气管上皮形成了身体对这种空气传播的污染物的第一道生理屏障，其中纤毛运动的功能是去除上覆粘液层中捕获的有害物质。驻留和浸润吞噬细胞也在此清除过程中发挥作用。在本文中，我们研究的作用，活性氧和氮的物种（ROS/RNS）的气道上皮细胞的反应颗粒。某些颗粒本身可以产生ROS，上皮细胞也可以，以响应适当的刺激。此外，气道和肺泡腔中的驻留巨噬细胞可以在吞噬吸入颗粒后释放ROS/RNS。这些巨噬细胞还释放大量的肿瘤坏死因子α（TNF-α），这是一种细胞因子，其可以依赖于细胞内ROS/RNS的产生而在气道上皮内产生应答。因此，信号转导途径启动，这可能导致气道中的炎症和其他病理生物学。这些作用包括细胞间粘附分子1、白细胞介素-6、胞质和诱导型一氧化氮合酶、锰超氧化物歧化酶、胞质磷脂酶A2的表达增加和粘液分泌过多。最终，ROS/RNS可能通过激活许多应答基因共有的激酶和转录因子，在气道上皮细胞对颗粒污染物的整体应答中发挥作用。因此，参与对有害颗粒物做出反应的防御机制可能导致复杂的级联事件，从而导致气道病理学。
Epidemiologic and occupational studies indicate adverse health effects due to inhalation of particulate air pollutants, but precise biologic mechanisms responsible have yet to be fully established. The tracheobronchial epithelium forms the body's first physiologic barrier to such airborne pollutants, where ciliary movement functions to remove the offending substances caught in the overlying mucus layer. Resident and infiltrating phagocytic cells also function in this removal process. In this paper, we examine the role of reactive oxygen and nitrogen species (ROS/RNS) in the response of airway epithelium to particulates. Some particulates themselves can generate ROS, as can the epithelial cells, in response to appropriate stimulation. In addition, resident macrophages in the airways and the alveolar spaces can release ROS/RNS after phagocytosis of inhaled particles. These macrophages also release large amounts of tumor necrosis factor alpha (TNF-alpha), a cytokine that can generate responses within the airway epithelium dependent upon intracellular generation of ROS/RNS. As a result, signal transduction pathways are set in motion that may contribute to inflammation and other pathobiology in the airway. Such effects include increased expression of intercellular adhesion molecule 1, interleukin-6, cytosolic and inducible nitric oxide synthase, manganese superoxide dismutase, cytosolic phospholipase A2, and hypersecretion of mucus. Ultimately, ROS/RNS may play a role in the global response of the airway epithelium to particulate pollutants via activation of kinases and transcription factors common to many response genes. Thus, defense mechanisms involved in responding to offending particulates may result in a complex cascade of events that can contribute to airway pathology.