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EFFECTS OF O3 AND NO2 ON HUMAN LUNG PROTEINS

O3 和 NO2 对人肺蛋白的影响

基本信息

批准号：
3253212
负责人：
David Andrew Johnson
金额：
$ 12.91万
依托单位：
EAST TENNESSEE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-07-01 至 1994-03-31
项目状态：
已结题

项目摘要

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.

肺蛋白是与吸入的空气污染物反应的明显目标该项目的重点是吸入的分子机制，氧化剂可能会损害对正常结构和功能至关重要的蛋白质肺人α-1蛋白酶的体外O3和NO2暴露抑制剂（α 1-PI）和支气管白细胞蛋白酶抑制剂（BLPI），通过抑制蛋白质降解来保护肺不受肺气肿的影响酶，将进行，以确定这些敏感性污染物氧化剂的抑制剂。抑制剂和不饱和烃的暴露碳氢化合物，以及膜截留抑制剂，将决定不饱和脂肪酸的自氧化是否有助于抑制剂失活;从而减少肺的防御。弹性蛋白是肺泡的主要结构蛋白，数据显示，O3和NO2直接改变了弹性蛋白的结构，它更容易被蛋白水解。该反应的机制将使用氨基酸分析、HPLC等技术进行研究肽图谱和电泳。类胰蛋白酶是人肥大细胞的主要颗粒蛋白。抗体类胰蛋白酶，与培养的小鼠中的类似蛋白质交叉反应肥大细胞瘤细胞，将用于研究O3和NO2对肥大细胞瘤细胞的影响。肥大细胞的脱粒，以检验氧化剂肥大细胞的诱导性脱颗粒导致了许多急性氧化剂对肺的生理影响。在鼻腔和鼻窦中观察到肥大细胞类胰蛋白酶水平升高，暴露于臭氧的人的支气管肺泡灌洗液。其他研究计划对O3和NO2的反应进行表征，并提供体内数据，用于解释培养的肥大细胞将获得有关O3的分子和细胞反应的知识， NO2，这可能导致更好的氧化剂暴露标记，并最终涉及干预或保护免受O3不利影响的方法， NO2。