Beers M F, Hamvas A, Moxley M A, Gonzales L W, Guttentag S H, Solarin K O, Longmore W J, Nogee L M, Ballard P L
Department of Medicine, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania, and the Institute for Environmental Medicine, USA.
Am J Respir Cell Mol Biol. 2000 Mar;22(3):380-91. doi: 10.1165/ajrcmb.22.3.3645.
Infants with inherited deficiency of pulmonary surfactant protein (SP) B develop respiratory failure at birth and die without lung transplantation. We examined aspects of surfactant metabolism in lung tissue and lavage fluid acquired at transplantation or postmortem from ten infants born at term with inherited deficiency of SP-B; comparison groups were infants with other forms of chronic lung disease (CLD) and normal infants. In pulse/chase labeling studies with cultured deficient tissue, no immunoprecipitable SP-B was observed and an approximately 6-kD form of SP-C accumulated that was only transiently present in CLD tissue. SP-B messenger RNA (mRNA) was approximately 8% of normal in deficient specimens, and some intact message was observed after, but not before, explant culture. Transcription rates for SP-B, assessed by nuclear run-on assay using probes for sequences both 5' and 3' of the common nonsense mutation (121ins2), were comparable in all lungs examined. The minimal surface tension achieved with lavage surfactant was similarly elevated in both deficient and CLD infants (26-31 mN/m) compared with normal infants (6 mN/m). Both SP-B-deficient and CLD infants had markedly decreased phosphatidylglycerol content of lavage and tissue compared with normal lung, whereas synthetic rates for phospholipids, including phosphatidylglycerol, were normal. We conclude that the mutated SP-B gene is transcribed normally but produces an unstable mRNA and that absence of SP-B protein blocks processing of SP-C. Chronic infant lung disease, of various etiologies, reduces surfactant function and apparently alters phosphatidylglycerol degradation.
患有遗传性肺表面活性物质蛋白（SP）B缺乏症的婴儿在出生时就会出现呼吸衰竭，若不进行肺移植则会死亡。我们研究了10名足月出生且患有遗传性SP - B缺乏症的婴儿在移植时或死后获取的肺组织和灌洗液中的表面活性物质代谢情况；对照组为患有其他形式慢性肺病（CLD）的婴儿和正常婴儿。在对培养的缺陷组织进行脉冲/追踪标记研究中，未观察到可免疫沉淀的SP - B，并且积累了一种约6-kD形式的SP - C，这种形式仅短暂存在于CLD组织中。在缺陷标本中，SP - B信使核糖核酸（mRNA）约为正常水平的8%，在外植体培养后而非培养前观察到一些完整的信使核糖核酸。通过使用针对常见无义突变（121ins2）5'和3'序列的探针进行核运行分析评估的SP - B转录率，在所有检查的肺中相当。与正常婴儿（6 mN/m）相比，缺陷婴儿和CLD婴儿灌洗表面活性物质达到的最小表面张力同样升高（26 - 31 mN/m）。与正常肺相比，SP - B缺乏婴儿和CLD婴儿的灌洗液和组织中磷脂酰甘油含量均显著降低，而包括磷脂酰甘油在内的磷脂合成率正常。我们得出结论，突变的SP - B基因转录正常，但产生不稳定的mRNA，并且SP - B蛋白的缺失会阻断SP - C的加工。各种病因导致的慢性婴儿肺病会降低表面活性物质功能，并明显改变磷脂酰甘油的降解。
