Abstract
Recent evidence indicates that surfactant deficiency may play a role in the pathophysiology of CDH, CTP:phosphocholine cytidylyltransferase (CT) catalyses a rate regulatory step in the de novo synthesis of surfactant phosphatidylcholine (PC) in type II pneumocytes (TII cells). Conditioned medium from fetal rat lung fibroblasts stimulated with 10−7 M Cortisol (FibCM) has been shown to increase surfactant PC synthesis in fetal TII cells through an increase of CT activity. Large left sided CDH with hypoplastic lungs were induced by feeding pregnant rats 100 mg Nitrofen on day 10 of gestation. Day 21 fetal TII cells and lung fibroblasts were isolated from control (no Nitrofen) and CDH fetuses. CT activity was significantly lower in homogenates from TII cells from CDH versus control lungs, whether CT was assayed in the absence (0.93±0.18 vs 1.27±0.28 nmol/min/mg protein; n = 8) or presence of 0.5mM PC/oleic acid (1/1) lipid vesicles (1.17 ± 0.21 vs 1.48±0.24; n=8). Choline3H-Me] incorporation into PC was studied in control TII cells incubated for 24h with FibCM. Compared to minimal essential medium with Cortisol, FibCM from control rats significantly stimulated PC synthesis (51.4 ±3.7 vs 60 ±3 × 104dpm/well; n= 10) but FibCM from CDH did not (54.7 ±3.3; n= 10).
We conclude that CT activity is significantly decreased in TII cells from CDH. In contrast to FibCM from controls, FibCM from CDH does not stimulate PC synthesis in TII cells. These data suggest that the immaturity of the fibroblasts may be primary responsible for decreased PC synthesis in CDH.
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Zimmermann, L., Ijsselstijn, H., Den Ouden, J. et al. 258 DECREASED SURFACTANT SYNTHESIS IN RATS WITH CONGENITAL DIAPHRAGMATIC HERNIA (CDH) IS DUE TO IMMATURITY OF BOTH TYPE II PNEUMOCYTES AND LUNG FIBROBLASTS. Pediatr Res 36, 45 (1994). https://doi.org/10.1203/00006450-199407000-00258
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DOI: https://doi.org/10.1203/00006450-199407000-00258