ADENOSINE-3',5'-MONOPHOSPHATE ANALOGS AND BETA-ADRENERGIC AGONISTS INDUCE THE SYNTHESIS OF THE MAJOR SURFACTANT APOPROTEIN IN HUMAN-FETAL LUNG INVITRO
ADENOSINE-3',5'-MONOPHOSPHATE ANALOGS AND BETA-ADRENERGIC AGONISTS INDUCE THE SYNTHESIS OF THE MAJOR SURFACTANT APOPROTEIN IN HUMAN-FETAL LUNG INVITRO
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DOI：
10.1210/endo-121-3-1155
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发表时间：
1987-09-01
期刊：
影响因子：
4.8
通讯作者：
MENDELSON, CR
中科院分区：
文献类型：
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作者：
ODOM, MJ;SNYDER, JM;MENDELSON, CR
使用β-已发现肾上腺素能激动剂治疗早产与早产新生儿呼吸窘迫综合征（RDS）发生率降低有关。β-激活腺苷酸环化酶并增加组织cAMP水平的拟交感神经药以及cAMP类似物刺激胎肺组织的表面活性剂甘油磷脂合成和分泌。在本研究中，我们使用针对主要的人肺表面活性物质脱辅基蛋白（一种35，000-道尔顿糖蛋白）的抗体来评价cAMP类似物二丁酰cAMP（Bt 2 cAMP）和β-cAMP的作用。肾上腺素能激动剂特布他林对器官培养中人胎肺外植体表面活性剂载脂蛋白合成的影响通过使用免疫印迹分析，我们发现，Bt 2cAMP（1 mM）显着刺激积累的主要表面活性剂载脂蛋白在人胎肺外植体，特布他林。Bt 2cAMP处理也增加了[35 S]蛋氨酸掺入主要表面活性剂脱辅基蛋白的相对速率。Bt 2cAMP诱导的表面活性剂载脂蛋白合成和积累的增加与可翻译的表面活性剂载脂蛋白mRNA水平的增加有关。应用光镜和电镜形态计量学方法研究了Bt 2cAMP对体外培养的人胎肺形态的影响。与Bt 2cAMP孵育48小时后，胎儿肺外植体的前肺泡管大大扩大，肺泡间结缔组织的相对量减少，与对照组织相比。在此时间点，Bt 2cAMP处理的外植体中II型细胞的体积密度显著大于对照外植体中的II型细胞的体积密度;然而，孵育4天和6天后，对照和Bt 2cAMP处理的组织中II型细胞的体积密度相似，并且对照组织的前肺泡管的管腔具有与Bt 2cAMP处理的外植体相似的体积密度。 Bt 2 cAMP对人胎肺外植体的超微结构形态也有显着影响。在Bt 2cAMP处理的组织的肺泡前导管的管腔中观察到大量分泌的板层体和管状髓鞘。对照组肺泡前导管管腔内板层小体少，无管状髓鞘。这些结果表明，cAMP可能在人胎肺主要表面活性物质载脂蛋白的合成和分泌中起重要的调节作用。
The use of .beta.-adrenergic agonists in the treatment of preterm labor has been found to be associated with a decreased incidence of respiratory distress syndrome (RDS) in premature newborns. .beta.-Sympathomimetic agents, which activate adenylate cyclase and increase tissue cAMP levels, as well as cAMP analogs stimulate surfactant glycerophospholipid synthesis and secretion by fetal lung tissue. In the present study, we used antibodies directed against the major human pulmonary surfactant apoprotein, a 35,000-dalton glycoprotein, to evaluate the effects of the cAMP analog dibutyryl cAMP (Bt2cAMP) and the .beta.-adrenergic agonist terbutaline on surfactant apoprotein synthesis in human fetal lung explants in organ culture. By use of immunoblot analysis, we found that Bt2cAMP (1 mM) markedly stimulated accumulation of the major surfactant apoprotein in human fetal lung explants, as did terbutaline. Bt2cAMP treatment also increased the relative rate of incorporation of [35S]methionine into the major surfactant apoprotein. The Bt2cAMP-induced increase in surfactant apoprotein synthesis and accumulation was associated with an increase in the levels of translatable surfactant apoprotein mRNA. Morphometric analysis at both the light and electron microscopic levels was used to evaluate the effects of Bt2cAMP on the morphology of the human fetal lung in vitro. After 48-h incubation with Bt2cAMP, the prealveolar ducts of the fetal lung explants were enlarged greatly, and the relative amount of interalveolar connective tissue was reduced compared to those in control tissues. The volume density of type II cells in the Bt2cAMP-treated explants was significantly greater than that in control explants at this time point; however, after 4 and 6 days of incubation, the volume density of type II cells in control and Bt2cAMP-treated tissues was similar, and the lumina of the prealveolar ducts of control tissues had a volume density similar to that of Bt2cAMP-treated explants. Bt2cAMP also had pronounced effects on the ultrastructural morphology of the human fetal lung explants. Large quantities of secreted lamellar bodies and tubular myelin were observed in the lumina of the prealveolar ducts of the Bt2cAMP-treated tissue. Few lamellar bodies and no tubular myelin were observed in the lumina of the prealveolar ducts of control tissues. These findings suggest that cAMP may serve an important regulatory role in the synthesis and secretion of the major surfactant apoprotein by human fetal lung.