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.
引用
收藏
相关论文
共 35 条
  • [31] Awasthi S., Coalson J.J., Crouch E., Yang F., King R.J., Surfactant proteins A and D in premature baboons with chronic lung injury (Bronchopulmonary dysplasia). Evidence for an inhibition of secretion, Am J Crit Care Med, 160, pp. 942-949, (1999)
  • [32] Woods E., Ohashi T., Polk D., Ikegami M., Ueda T., Jobe A.H., Surfactant treatment and ventilation effects on surfactant SP-A, SP-B,and SP-C mRNA levels in preterm lamb lungs, Am J Physiol, 269, (1995)
  • [33] Beresford M.W., Shaw N.J., Bronchoalveolar lavage surfactant protein A, B, and D concentrations in preterm infants ventilated for respiratory distress syndrome receiving natural and synthetic surfactants, Pediatr Res, 53, pp. 663-670, (2003)
  • [34] Merrill J.D., Ballard R.A., Cnaan A., Hibbs A.M., Godinez R.I., Godinez M.H., Truog W.E., Ballard P.L., Dysfunction of pulmonary surfactant in chronically ventilated premature infants, Pediatr Res, 56, pp. 918-926, (2004)
  • [35] Hallman M., Merritt T.A., Akino T., Bry K., Surfactant protein A, phosphatidylcholine, and surfactant inhibitors in epithelial lining fluid: Correlation with surface activity, severity of respiratory distress syndrome, and outcome in small premature infants, Am Rev Respir Dis, 144, pp. 1376-1384, (1991)
1234