EFFECTS OF O3 AND NO2 ON HUMAN LUNG PROTEINS

O3 和 NO2 对人肺蛋白的影响

• 批准号: 3253210
• 负责人: David Andrew Johnson
• 金额: $ 13.53万
• 依托单位: EAST TENNESSEE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3253210
• 关键词: adduct; air pollution; autoradiography; chemical fingerprinting; diagnostic respiratory lavage; elastin; emphysema; enzyme linked immunosorbent assay; enzyme mechanism; gel electrophoresis; high performance liquid chromatography; human subject; lung; mast cell; membrane proteins; ozone; peroxidation; pollution related respiratory disorder; protease inhibitor; protective chemical group; protein sequence; protein structure function; proteolysis; respiratory protein

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.

肺蛋白是与吸入空气污染物发生反应的明显靶点