Ridsdale Ross, Roth-Kleiner Matthias, D'Ovidio Frank, Unger Sharon, Yi Man, Keshavjee Shaf, Tanswell A Keith, Post Martin
Lung Biology Program, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Am J Respir Crit Care Med. 2005 Jul 15;172(2):225-32. doi: 10.1164/rccm.200501-109OC. Epub 2005 May 5.
Two common lung-related complications in the neonate are respiratory distress syndrome, which is associated with a failure to generate low surface tension at the air-liquid interface because of pulmonary surfactant insufficiency, and bronchopulmonary dysplasia (BPD), a chronic lung injury with reduced alveolarization. Surfactant phosphatidylcholine (PC) molecular species composition during alveolarization has not been examined. Mass spectrometry analysis of bronchoalveolar lavage fluid of rodents and humans revealed significant changes in surfactant PC during alveolar development and BPD. In rats, total PC content rose during alveolarization, which was caused by an increase in palmitoylmyristoyl-PC (16:0/14:0PC) concentration. Furthermore, two animal models of BPD exhibited a specific reduction in 16:0/14:0PC content. In humans, 16:0/14:0PC content was specifically decreased in patients with BPD and emphysema compared with patients without alveolar pathology. Palmitoylmyristoyl-PC content increased with increasing intrinsic surfactant curvature, suggesting that it affects surfactant function in the septating lung. The changes in acyl composition of PC were attributed to type II cells producing an altered surfactant during alveolar development. These data are compatible with extracellular surfactant 16:0/14:0PC content being an indicator of alveolar architecture of the lung.
新生儿常见的两种肺部相关并发症是呼吸窘迫综合征,其与由于肺表面活性物质不足而导致在气液界面产生低表面张力失败有关,以及支气管肺发育不良(BPD),一种肺泡化减少的慢性肺损伤。肺泡化过程中表面活性物质磷脂酰胆碱(PC)分子种类组成尚未得到研究。对啮齿动物和人类支气管肺泡灌洗液的质谱分析显示,在肺泡发育和BPD期间表面活性物质PC有显著变化。在大鼠中,肺泡化过程中总PC含量升高,这是由棕榈酰肉豆蔻酰-PC(16:0/14:0PC)浓度增加引起的。此外,两种BPD动物模型显示16:0/14:0PC含量有特异性降低。在人类中,与无肺泡病变的患者相比,BPD和肺气肿患者的16:0/14:0PC含量特异性降低。棕榈酰肉豆蔻酰-PC含量随着内源性表面活性物质曲率增加而增加,表明它影响分隔肺中的表面活性物质功能。PC酰基组成的变化归因于II型细胞在肺泡发育过程中产生改变的表面活性物质。这些数据与细胞外表面活性物质16:0/14:0PC含量是肺肺泡结构指标这一观点相符。