Spatial and temporal expression of surfactant proteins in hyperoxia-induced neonatal rat lung injury

被引：22
作者：
ter Horst S.A.J. [1 ]
Fijlstra M. [1 ]
Sengupta S. [1 ]
Walther F.J. [1 ,2 ]
Wagenaar G.T.M. [1 ]
机构：
[1] Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, 2333 ZA Leiden
[2] Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA 90502
来源：
BMC Pulmonary Medicine | / 6卷 / 1期
关键词：
Surfactant Protein; Alveolar Type; Clara Cell; Adult Lung; Clara Cell Secretory Protein;
D O I：
10.1186/1471-2466-6-8
中图分类号：
学科分类号：
摘要：
Background: Bonchopulmonary 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. Conclusion: 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. © 2006 ter Horst et al: licensee BioMed Central Ltd.
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  • [1] Jobe A.H., The new BPD: An arrest of lung development, Pediatr Res, 46, pp. 641-643, (1999)
  • [2] Bancalari E., Gonzalez A., Clinical course and lung function abnormalities during development of neonatal chronic lung disease, Chronic Lung Disease in Early Infancy, (2000)
  • [3] Jobe A.H., Bancalari E., Bronchopulmonary Dysplasia, Am J Respir Crit Care Med, 163, pp. 1723-1729, (2001)
  • [4] Coalson J.J., Experimental models of bronchopulmonary dysplasia, Biol Neonate, 71, pp. 35-38, (1997)
  • [5] Warner B.B., Stuart L.A., Papes R.A., Wispe J.R., Functional and pathological effects of prolonged hyperoxia in neonatal mice, Am J Physiol, 275, (1998)
  • [6] Roberts R.J., Weesner K.M., Bucher J.R., Oxygen-induced alterations in lung vascular development in the newborn rat, Pediatr Res, 17, pp. 368-375, (1983)
  • [7] Han R.N.N., Buch S., Tseu I., Youngh J., Christie N.A., Frndova H., Lye S.J., Post M., Tanswell A.K., Changes in structure, mechanics and insulin-like growth factor-related gene expression in the lungs of newborn rats exposed to air or 60% oxygen, Pediatr Res, 39, pp. 921-929, (1996)
  • [8] Chen Y., Martinez M.A., Frank L., Prenatal dexamethasone administration to premature rats exposed to prolonged hyperoxia: A new rat model of pulmonary fibrosis (bronchopulmonary dysplasia), J Pediatr, 130, pp. 409-416, (1997)
  • [9] Wagenaar G.T.M., ter Horst S.A., Van Gastelen M.A., Leijer L.M., Mauad T., van der Velden P.A., de Heer E., Hiemstra P.S., Poorthuis B.J.H.M., Walther F.J., Gene expression profile and histopathology of experimental bronchopulmonary dysplasia induced by prolonged oxidative stress, Free Radic Bio Med, 36, pp. 782-801, (2004)
  • [10] Clark C., Clark L.S., The genetics of neonatal respiratory disease, Semin Fetal Neonatal Med, 10, pp. 271-282, (2005)
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