MECHANISMS OF AIR POLLUTANT INDUCED AIRWAY PERMEABILITY

空气污染物对呼吸道上皮通透性的影响 例如臭氧和烟草烟雾。尽管事实是这样的 渗透性的变化可能是有害的，基本的 这种现象背后的机制并不是很好 明白了。在我们之前的机理研究中，臭氧诱导 通透性、转运途径和细胞骨架的变化 类似于由应用微丝引起的变化 不稳定剂细胞松弛素D。 我们现在建议扩大这项研究的范围，包括对 炎性细胞，炎性细胞或 上皮细胞和各种细胞产物的抑制物 涉及空气污染物对呼吸道通透性的影响， 细胞骨架、紧密连接和运输途径。 炎症细胞一旦被激活，就可能在气管内聚集。 和肺泡粘膜以及调节呼吸道的释放产物 和血管通透性，并改变细胞的细胞骨架 肺内皮细胞或上皮细胞。人体细胞骨架的研究 结合上皮细胞，中性粒细胞， 或他们的产品，因此有望改善我们的 了解渗透率变化的机理。 渗透率和持续时间增加的时间序列 将研究气管和支气管肺泡区，以及 通透性的改变将与炎症相关 反应、细胞骨架改变、紧密连接改变和 气管和肺泡内示踪剂运输的结构途径 在：(1)只暴露于空气、臭氧(0.6ppm)或臭氧(0.6ppm)的大鼠 NO2(2.5ppm)，以及(2)暴露于这些气体的大鼠，以及 用(A)神经中性粒细胞的氧化产物(超氧化物， 过氧化氢，羟基自由基)，(B)抗氧化剂(牛磺酸， 过氧化氢酶、超氧化物歧化酶和二甲基硫脲，(C)抗- 炎性药物(甲帕克林和甲基强的松龙)，(D) 花生四烯酸代谢产物(白三烯和 前列腺素)或其抑制剂(FPL 55712、BW 755C和 吲哚美辛)、(E)细胞骨架不稳定剂及其 组合(秋水仙碱、长春花碱、细胞松弛素D和 秋水仙素细胞松弛素D)。 中性粒细胞在呼吸道通透性中的作用也将是 通过研究通透性和炎症进行评估 未暴露的粒细胞减少性注射分离的中性粒细胞 或03只摘除近交系大鼠。 涉及离体肺泡摄取示踪剂的其他研究 II型细胞，中性粒细胞与II型细胞的黏附 细胞骨架在体内改变的条件下的变化 如上所述的渗透性，也将增加我们的 对示踪剂运输机制的理解。

Airway epithelial permeability is altered by airborne pollutants such as ozone and tobacco smoke. Despite the fact that such changes in permeability may be detrimental, the basic mechanisms that underlie this phenomenon are not well understood. In our previous mechanistic studies, ozone-induced changes in permeability, transport pathway and cytoskeleton were similar to changes induced by application of the microfilament destabilizing agent cytochalasin D. We now proposed to broaden this study by including an analysis of inflammatory cells, the products of inflammatory cells or epithelial cells, and various inhibitors of cell products as they relate to air pollutant effects on airway permeability, cytoskeleton, tight junctions and transport pathway. Inflammatory cells, upon activation, may aggregate in tracheal and alveolar mucosa and release products that modulate airway and vascular permeability and modify the cytoskeleton of cells in pulmonary endothelia or epithelia. A study of the cytoskeleton in combination with an investigation of epithelial cells, neutrophils, or their products, is therefore expected to improve our understanding of the mechanisms of permeability changes. The time sequence of increased permeability and duration in the tracheal and bronchoalveolar region will be studied, and permeability changes will be correlated with inflammatory response, cytoskeletal changes, tight junction alterations and structural pathways of tracer transport in the trachea and alveoli in: (1) rats exposed to air only or O3(O.6 ppm) or O3 (O.6 ppm) + NO2 (2.5 ppm), and (2) rats exposed to these gases and also treated with (a) oxidant products of neurotrophils (superoxide, hydrogen peroxide, hydroxyl radicals), (b) antioxidants (taurine, catalase, superoxide dismutase and dimethylthiourea, (c) anti- inflammatory drugs (mapacrine and methyl prednisolone), (d) products of arachidonic acid metabolism (leukotrienes and prostaglandins) or their inhibitors (FPL 55712, BW 755C and indomethacin), (e) cytoskeleton destabilizers and their combinations (colchicine, vinblastine ,cytochalasin D and colchicine + cytochalasin D). The role of neutrophils in airway permeability will also be assessed by studying permeability and inflammation following injection of isolated neutrophils into granulocytopenic unexposed or 03 expsoed inbred rats. Additional studies involving uptake of tracers by isolated alveolar type II cells, adherence of neutrophils to type II cells and cytoskeletal changes under conditions that alter in vivo permeability described above, will also be done to add to our understanding of the mechanisms of tracer transport.