Anti-bombesin monoclonal antibodies modulate fetal mouse lung growth and maturation in utero and in organ cultures.
Anti-bombesin monoclonal antibodies modulate fetal mouse lung growth and maturation in utero and in organ cultures.
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抗铃蟾肽单克隆抗体可调节胎儿小鼠肺在子宫内和器官培养物中的生长和成熟。
DOI：
10.1002/ar.1092360107
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Torday,JS
中科院分区：
文献类型：
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作者：
Sunday,ME;Hua,J;Reyes,B;Masui,H;Torday,JS
胎肺神经内分泌细胞（PNEC）含有丰富的胃泌素释放肽（GRP，哺乳动物铃蟾肽样肽[BLP]）。以前，添加蛙皮素导致增加胎儿肺的生长和成熟在子宫内和器官培养。蛙皮素单克隆抗体（mAb）（2A 11）阻断了无血清培养基中肺器官培养物的基线自动饱和。在本研究中，我们分析了从妊娠第15-18天每天在子宫内施用2A 11后的肺发育。与用MOPC（一种无反应性mAb）处理的对照组相比，用2A 11处理然后在第18天收获的胎肺显示表面活性剂磷脂合成的剂量依赖性降低。然而，在第17天收获的2A 11处理的胎肺显示3 H-胆碱掺入饱和磷脂酰胆碱、3 H-胸苷掺入DNA和分化的II型肺细胞的相对数量的矛盾增加。在含血清的第17天肺器官培养物中，2A 11刺激胆碱和胸苷掺入。由于表皮生长因子（EGF）是除了蛙皮素之外唯一已知刺激胎肺生长和成熟的药物，我们将EGF添加到无血清培养物中并重建刺激作用。在含血清的培养物中，鼠EGF受体mAb（ERA）阻断了2A 11诱导的肺生长和成熟，并且通过添加EGF克服了这种效应。在体内，ERA还在第17天阻断2A 11对胎肺的刺激作用。这些观察结果表明，如果第17天BLP水平降低，EGF受体上调可能会维持肺的生长和成熟。尽管如此，BLP似乎参与了第18天的肺成熟，支持PNEC在正常肺发育中的作用。© 1993 Wiley利斯公司
Fetal pulmonary neuroendocrine cells (PNECs) contain abundant gastrin‐releasing peptide (GRP, mammalian bombesin‐like peptide [BLP]). Previously, addition of bombesin resulted in increased fetal lung growth and maturation in utero and in organ cultures. A monoclonal antibody (mAb) to bombesin (2A11) blocked baseline automaturation of lung organ cultures in serum‐free medium. In the present study, we analyze lung development following daily in utero administration of 2A11 from gestational days 15–18. Fetal lung treated with 2A11 and then harvested on day 18 demonstrated a dose‐dependent decrease in surfactant phospholipid synthesis compared to controls treated with MOPC, an unreactive mAb. However, 2A11‐treated fetal lung harvested on day 17 showed paradoxical increases in3H‐choline incorporation into saturated phosphatidylcholine,3H‐thymidine incorporation into DNA, and relative numbers of differentiated type II pneumocytes. In serum‐containing day 17 lung organ cultures, 2A11 stimulated choline and thymidine incorporation. Since epidermal growth factor (EGF) is the only agent besides bombesin known to stimulate both fetal lung growth and maturation, we added EGF to serum‐free cultures and reconstituted the stimulatory effects. A murine EGF receptor mAb (ERA) blocked 2A11‐induced lung growth and maturation in serum‐containing cultures, and this effect was overcome by adding EGF. In vivo, ERA also blocked stimulatory effects of 2A11 in fetal lung on day 17. These observations suggest that EGF receptor up‐regulation may maintain lung growth and maturation if BLP levels are diminished on day 17. Nonetheless, BLPs appear to be involved in lung maturation on day 18, supporting a role for PNECs in normal lung development. © 1993 Wiley‐Liss, Inc.