EFFECTS OF O3 AND NO2 ON HUMAN LUNG PROTEINS

肺蛋白质显然是与吸入空气污染物反应的目标 该项目的重点是吸入的分子机制 氧化剂可能会破坏对正常结构和功能至关重要的蛋白质 肺部。人α-1蛋白水解酶体外暴露于O_3和NO_2的研究 抑制物(α1-PI)和支气管白细胞蛋白酶抑制物(BLPI)， 通过抑制蛋白质降解来保护肺部免受肺气肿的侵袭 酶，将被用来确定这些细菌的敏感性 污染物氧化剂的抑制剂。抑制剂和不饱和化合物的暴露 碳氢化合物以及膜包埋的抑制剂将决定 不饱和脂肪酸的自氧化是否有助于 抑制物失活；从而降低肺的防御能力。 弹性蛋白是肺泡的主要结构蛋白，初步认为 数据显示，臭氧和亚硝酸盐直接改变弹性蛋白的结构，使 它更容易被蛋白质分解。该反应的机理(S)(S) 将使用氨基酸分析、高效液相色谱等技术进行研究 多肽图谱和电泳法。 类胰蛋白酶是人类肥大细胞的主要颗粒蛋白。抗体 在培养的小鼠中，它与类似的蛋白质发生交叉反应 肥大细胞瘤细胞，将被用来研究臭氧和亚硝酸盐对细胞的影响。 肥大细胞脱颗粒，以检验氧化剂 肥大细胞的诱导脱颗粒是许多急性 氧化剂对肺的生理影响。 在鼻腔和鼻腔中观察到肥大细胞类胰蛋白酶水平的增加 接触臭氧的人的支气管肺泡灌洗液。其他研究 计划用来描述这种对臭氧和二氧化氮的反应，并 为解释体外培养结果提供体内数据 肥大细胞。 将获得关于臭氧和臭氧的分子和细胞反应的知识 NO2，这可能会导致更好的氧化剂暴露标志，并最终 关于干预或保护免受臭氧和 第二名。

Lung proteins are obvious targets for reaction with inhaled air pollutants and the project focuses on the molecular mechanisms by which inhaled oxidants may damage proteins vital to the normal structure and function of the lung. In vitro O3 and NO2 exposures of human alpha-1proteinase inhibitor (alpha1-PI) and bronchial leukocyte proteinase inhibitor (BLPI), which protect the lung from emphysema by inhibiting protein degrading enzymes, will be performed to determine the susceptibility of these inhibitors to pollutant oxidants. Exposures of inhibitors and unsaturated hydrocarbons, as well as membrane entrapped inhibitors, will determine whether the autoxidation of unsaturated fatty acids contributes to inhibitor inactivation; thus diminishing the lung's defenses. Elastin is the major structural protein of the lung alveoli and preliminary data show that O3 and NO2 directly alter the structure of elastin and make it more susceptible to proteolysis. The mechanism(s) of this reaction(s) will be investigated using techniques such as amino acid analysis, HPLC peptide mapping and electrophoresis. Tryptase is the principal granular protein of human mast cells. Antibodies to tryptase, that cross-react with a similar protein in cultured mouse mastocytoma cells, will be used to study the effects of O3 and NO2 on the degranulation of the mast cells, to test the hypothesis that oxidant induced degranulation of mast cells accounts for many of the acute physiological effects of oxidants on the lung. Increased levels of mast cell tryptase have been observed in nasal and bronchoalveolar lavage fluids from O3-exposed humans. Additional studies are planned to characterize this response with regard to O3 and NO2, and to provide in vivo data for interpretation of in vitro results with cultured mast cells. Knowledge will be gained on the molecular and cellular reactions of O3 and NO2, which could lead to better markers of oxidant exposure and eventually to methods of intervention or protection from the adverse effects of O3 and NO2.