Abstract
BackgroundBronchopulmonary 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.MethodsWe 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.ResultsGene 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.ConclusionThe 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.
Highlights
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
In our laboratory we investigate the pathophysiology of bronchopulmonary dysplasia (BPD) to develop new treatment modalities for this chronic lung disease, using the hyperoxia-exposed preterm rat as a model for experimental Bronchopulmonary dysplasia (BPD) [9,23]
Peak levels were observed in adult lungs for surfactant proteins (SP)-A, SP-C and CC10
Summary
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. BPD is defined clinically by the need for extra oxygen at 36 weeks of gestation, and mainly affects infants born at less than 30 weeks of gestation with a birth weight less than 1,200 g [1,2] This multifactorial chronic lung disease is characterized by decreased alveolarization and abnormal vascularization and associated with surfactant deficiency, oxidative stress, barotrauma, inflammation, alveolar fibrin deposition, nutrition, and genetic background [1,3]. Various studies have reported the expression of surfactant proteins and CC10 during normal development and under pathological conditions [16,17,18,19,20,21,22], but the temporal and spatial distribution patterns of the mRNAs of SP-A, -B, -C and -D and CC10 during normal postnatal lung development and in prolonged hyperoxia in the rat are not fully established. The increased expression of SP-A mRNA during exposure to hyperoxia could be attributed to an induction of SP-A expression in bronchial epithelial Clara cells
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