Pulmonary surfactant metabolism in infants lacking surfactant protein B
Pulmonary surfactant metabolism in infants lacking surfactant protein B
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DOI：
10.1165/ajrcmb.22.3.3645
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发表时间：
2000-03-01
影响因子：
6.4
通讯作者：
Ballard, PL
中科院分区：
文献类型：
--
作者：
Beers, MF;Hamvas, A;Ballard, PL
患有遗传性肺表面活性物质蛋白（SP）B缺乏的婴儿在出生时会出现呼吸衰竭，若不进行肺移植就会死亡。我们检测了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尸检时获取的肺组织和灌洗液中表面活性物质代谢的相关情况；对照组为患有其他形式慢性肺部疾病（CLD）的婴儿和正常婴儿。在对培养的缺陷组织进行脉冲/追踪标记研究时，未观察到可免疫沉淀的SP - B，且有一种约6 - kD的SP - C形式积聚，这种形式在CLD组织中只是短暂存在。在缺陷样本中，SP - B信使RNA（mRNA）约为正常水平的8%，在移植组织培养后（而非培养前）观察到一些完整的信息。通过核连缀分析，使用针对常见无义突变（121ins2）5'和3'序列的探针评估SP - B的转录速率，在所有检测的肺中是相当的。与正常婴儿（6 mN/m）相比，缺陷婴儿和CLD婴儿的灌洗表面活性物质所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缺乏的婴儿和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速率是正常的。我们得出结论：突变的SP - B基因正常转录，但产生不稳定的mRNA，并且SP - B蛋白的缺失会阻碍SP - C的加工。各种病因导致的婴儿慢性肺部疾病会降低表面活性物质的功能，并明显改变磷脂酰甘油的降解。
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.