Abstract
Proteinase-activated receptor 2 (PAR2), a G-protein-coupled receptor activated by serine proteinases such as trypsin, has been suggested to play an important role in inflammatory and fibroproliferative processes. In preterm infants, the development of bronchopulmonary dysplasia (BPD) is characterized by early pulmonary inflammation and subsequent interstitial fibrosis. High pulmonary trypsin-2 has been shown to be associated with the development of BPD. We studied the expression and distribution of PAR2 and trypsin-2 by immunohistochemistry in autopsy lung specimens of fetuses (n = 10), of preterm infants who died of acute or prolonged respiratory distress syndrome (RDS) (n = 8 and n = 7, respectively) or BPD (n = 6), and of newborn infants without lung disease (n = 5) who served as controls. In prolonged RDS and BPD, PAR2 immunoreactivity was significantly higher in bronchial epithelium when compared with infants without pulmonary pathology (p < 0.05 and p < 0.005, respectively). In alveolar epithelium, expression of PAR2 was elevated in prolonged RDS when compared with newborn infants without pulmonary pathology (p < 0.05). Moreover, strong expression of PAR2 was detected in myofibroblasts of thickened and fibrotic alveolar walls in prolonged RDS or BPD. Trypsin-2 was co-localized with PAR2 in bronchoalveolar epithelium. These findings suggest that PAR2, possibly activated by trypsin-2, may participate in inflammation and fibroproliferation associated with progression of RDS toward BPD in preterm infants.
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Abbreviations
- BPD:
-
Bronchopulmonary dysplasia
- PAR2:
-
Proteinase-activated receptor 2
- RDS:
-
Respiratory distress syndrome
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Acknowledgements
The authors thank Prof. Seppo Sarna, Ph.D., for his help with statistical analysis of the data, and Elina Laitinen and Päivi Peltokangas for excellent technical assistance.
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Supported by grants from the Foundation for the Pediatric Research, Finska Läkaresällskapet, the Sigrid Jusélius Foundation, the Helsinki University Central Hospital Research Fund and the Canadian Institutes of Health Research (MDH).
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Cederqvist, K., Haglund, C., Heikkilä, P. et al. High Expression of Pulmonary Proteinase-activated Receptor 2 in Acute and Chronic Lung Injury in Preterm Infants. Pediatr Res 57, 831–836 (2005). https://doi.org/10.1203/01.PDR.0000161416.63314.70
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DOI: https://doi.org/10.1203/01.PDR.0000161416.63314.70
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