Ramsay P L, DeMayo F J, Hegemier S E, Wearden M E, Smith C V, Welty S E
Department of Pediatrics, Baylor College of Medicine, Houston Texas, USA.
Am J Respir Crit Care Med. 2001 Jul 1;164(1):155-61. doi: 10.1164/ajrccm.164.1.2008022.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects prematurely born infants and appears to evolve in part from early inflammatory responses in the lung. The inflammatory responses have been associated with protein and lipid oxidation in tracheal aspirate fluids. The present study was designed to test the hypothesis that in the first week of life specific oxidations and/ or altered expressions of proteins would be observed in tracheal aspirate fluids in infants who would subsequently develop BPD. We obtained tracheal aspirate fluids on Days of life 1, 3, and 6 from infants born at < or = 29 wk gestation, incubated the fluids with 2,4-dinitrophenylhyrazine (DNPH), separated the proteins electrophoretically, and assessed DNPH reactivity by immunonblots. DNPH reactivity of a protein that was identified as Clara cell secretory protein (CCSP) was observed more consistently in tracheal aspirate fluids from infants who later developed BPD than from infants who did not develop BPD. Tracheal aspirate fluid levels of immunoreactive CCSP were also lower on Day of life 1 in infants who developed BPD than in those who did not develop BPD. Increased CCSP oxidation and decreased immunoreactive CCSP expression in infants who subsequently developed BPD suggest that Clara cell function and CCSP expression may be critical for normal bronchoalveolar fluid homeostasis and that maintaining CCSP expression and function may be useful goals for targeted therapies for inhibition of the development of BPD.
支气管肺发育不良(BPD)是一种影响早产儿的慢性肺部疾病,其部分病因似乎源于肺部早期的炎症反应。这些炎症反应与气管吸出液中的蛋白质和脂质氧化有关。本研究旨在验证以下假设:在出生后的第一周,随后会发生BPD的婴儿的气管吸出液中会观察到特定的氧化反应和/或蛋白质表达改变。我们从孕周小于或等于29周的婴儿出生后第1、3和6天获取气管吸出液,将这些液体与2,4-二硝基苯肼(DNPH)一起孵育,通过电泳分离蛋白质,并通过免疫印迹评估DNPH反应性。与未发生BPD的婴儿相比,在随后发生BPD的婴儿的气管吸出液中,更一致地观察到一种被鉴定为克拉拉细胞分泌蛋白(CCSP)的蛋白质的DNPH反应性。在出生后第1天,发生BPD的婴儿的气管吸出液中免疫反应性CCSP水平也低于未发生BPD的婴儿。随后发生BPD的婴儿中CCSP氧化增加和免疫反应性CCSP表达降低表明,克拉拉细胞功能和CCSP表达可能对正常支气管肺泡液稳态至关重要,维持CCSP表达和功能可能是抑制BPD发展的靶向治疗的有用目标。