Ijsselstijn H, Gaillard J L, de Jongste J C, Tibboel D, Cutz E
Department of Pediatric Surgery, Erasmus University and University Hospital/Sophia Children's Hospital, Rotterdam, The Netherlands.
Pediatr Res. 1997 Nov;42(5):715-20. doi: 10.1203/00006450-199711000-00026.
Infants with congenital diaphragmatic hernia (CDH) have a high neonatal mortality and morbidity owing to lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells produce bombesin-like peptide (BLP), a peptide with growth factor-like properties involved in lung development. We examined the expression of BLP immunostaining in pulmonary neuroendocrine cells (PNEC), and in clusters of these cells called neuroepithelial bodies (NEB), in the lungs of three groups of infants: patients with CDH, newborns with lung hypoplasia due to other causes, and control subjects without lung abnormalities. Morphometric analysis included: 1) percent immunostained airways; 2) percent immunostained epithelium (i.e. frequency of PNEC and NEB); and 3) NEB size. Controls and infants with lung hypoplasia did not differ with respect to BLP immunostaining. The ipsilateral and the contralateral lungs in CDH had a similar BLP immunostaining pattern of PNEC and NEB. The BLP immunostaining varied between CDH cases, possibly due to the differences in clinical presentation. The mean NEB size was significantly increased in infants with CDH compared with the other two groups (p = 0.02). Some CDH cases with large NEBs also showed a high percentage of immunostained epithelium. Lung-body weight ratio correlated positively with percent immunostained airways, and negatively with the NEB size. We conclude that in lungs of CDH patients BLP immunostaining in PNEC and NEB differs from that of infants with lung hypoplasia due to other causes and controls. The increased BLP immunostaining observed in some cases of CDH might reflect a compensatory mechanism related to impaired lung development and/or failure of neuropeptide secretion during neonatal adaptation.
患有先天性膈疝(CDH)的婴儿由于肺发育不全和持续性肺动脉高压,新生儿死亡率和发病率很高。肺神经内分泌细胞产生蛙皮素样肽(BLP),这是一种具有生长因子样特性的肽,参与肺发育。我们检测了三组婴儿肺部肺神经内分泌细胞(PNEC)及其细胞簇即神经上皮小体(NEB)中BLP免疫染色的表达情况,这三组婴儿分别为:CDH患者、因其他原因导致肺发育不全的新生儿以及无肺部异常的对照受试者。形态计量分析包括:1)免疫染色气道的百分比;2)免疫染色上皮的百分比(即PNEC和NEB的频率);3)NEB大小。对照组和肺发育不全的婴儿在BLP免疫染色方面没有差异。CDH婴儿的同侧和对侧肺中PNEC和NEB的BLP免疫染色模式相似。CDH病例之间的BLP免疫染色有所不同,可能是由于临床表现的差异。与其他两组相比,CDH婴儿的平均NEB大小显著增加(p = 0.02)。一些NEB较大的CDH病例也显示出较高百分比的免疫染色上皮。肺与体重比与免疫染色气道的百分比呈正相关,与NEB大小呈负相关。我们得出结论,CDH患者肺部PNEC和NEB中的BLP免疫染色与因其他原因导致肺发育不全的婴儿及对照组不同。在一些CDH病例中观察到的BLP免疫染色增加可能反映了一种与肺发育受损和/或新生儿适应过程中神经肽分泌失败相关的代偿机制。