Spatial and temporal expression of surfactant proteins in hyperoxia-induced neonatal rat lung injury.
BACKGROUND
Bronchopulmonary dysplasia, a complex chronic lung disease in premature children in which oxidative stress and surfactant deficiency play a crucial role, is characterized by arrested alveolar and vascular development of the immature lung. The spatial and temporal patterns of expression of surfactant proteins are not yet fully established in newborn infants and animal models suffering from BPD.


METHODS
We studied the mRNA expression of surfactant proteins (SP) A, -B, -C and -D and Clara cell secretory protein (CC10) with RT-PCR and in situ hybridization and protein expression of CC10, SP-A and -D with immunohistochemistry in the lungs of a preterm rat model, in which experimental BPD was induced by prolonged oxidative stress.


RESULTS
Gene expression of all surfactant proteins (SP-A, -B, -C and -D) was high at birth and initially declined during neonatal development, but SP-A, -B, and -D mRNA levels increased during exposure to hyperoxia compared to room-air controls. Peak levels were observed in adult lungs for SP-A, SP-C and CC10. Except for SP-A, the cellular distribution of SP-B, -C, -D and CC10, studied with in situ hybridization and/or immunohistochemistry, did not change in room air nor in hyperoxia. Exposure to normoxia was associated with high levels of SP-A mRNA and protein in alveolar type 2 cells and low levels in bronchial Clara cells, whereas hyperoxia induced high levels of SP-A expression in bronchial Clara cells.


CONCLUSIONS
The increased expression of SP-A mRNA under hyperoxia can be attributed, at least in part, to an induction of mRNA and protein expression in bronchial Clara cells. The expanded role of Clara cells in the defence against hyperoxic injury suggests that they support alveolar type 2 cell function and may play an important role in the supply of surfactant proteins to the lower airways.
ter Horst
Simone A J
SA
Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, J6-S, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. s.a.j.ter_horst@lumc.nl
Fijlstra
Margot
M
Sengupta
Sujata
S
Walther
Frans J
FJ
Wagenaar
Gerry T M
GT
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D018496:Hyperoxia / Q000150:complications*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism; D037661:Pulmonary Surfactant-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014018:Tissue Distribution; D014598:Uteroglobin / Q000235:genetics / Q000378:metabolism
D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D012333:RNA, Messenger; C556391:Scgb1a1 protein, rat; D014598:Uteroglobin