Pulmonary Trypsin-2 in the Development of Bronchopulmonary Dysplasia in Preterm Infants

Abstract

Objectives. In the preterm infant, lung injury can lead to irreversible tissue destruction and abnormal lung development. We examined whether pulmonary trypsin, a potent matrix-degrading serine proteinase and proteinase-cascade activator, is associated with the development of bronchopulmonary dysplasia (BPD) in preterm infants. Methods. Samples of tracheal aspirate fluid were collected from 32 intubated preterm infants during their first 2 postnatal weeks. The presence and molecular forms of trypsin in tracheal aspirate fluid samples were analyzed by zymography and Western blotting. The concentrations of trypsinogen-1 and -2 and tumor-associated trypsin inhibitor were measured by immunofluorometry. For examining the expression of trypsin-2 in lung tissue, immunohistochemistry was performed on autopsy specimens of fetuses, of preterm infants who died from respiratory distress syndrome or BPD, and of term infants without lung injury. Results. In infants who subsequently developed BPD (n = 18), we detected significantly higher concentrations of trypsinogen-2 during postnatal days 5 to 10 compared with those who survived without it. There was no difference in trypsinogen-1 concentrations. Tumor-associated trypsin inhibitor concentrations were significantly lower in infants who needed mechanical ventilation for >1 week. Immunohistochemistry demonstrated that trypsin-2 was predominantly expressed in bronchial and bronchiolar epithelium. In 2 preterm infants who died from prolonged respiratory distress syndrome, trypsin-2 was also expressed in vascular endothelium. Conclusions. The levels of trypsinogen-2 are higher during postnatal days 5 to 10 in infants who subsequently develop BPD. The results suggest that high levels of pulmonary trypsin-2 may be associated with the development of BPD. This raises the possibility that therapy with exogenous proteinase inhibitors might prevent the development of BPD in preterm infants with respiratory distress.