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.

• Authors: Katariina Cederqvist, Caj Haglund, Päivi Heikkilä, Timo Sorsa, Taina Tervahartiala, Ulf-Håkan Stenman, Sture Andersson
• Journal: Pediatrics (Pediatrics) Vol. 112 Issue 3 Pt 1 Pg. 570-7 (Sep 2003) ISSN: 1098-4275 [Electronic] United States
• PMID: 12949286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• PRSS2 protein, human
• Trypsin Inhibitor, Kazal Pancreatic
• Trypsinogen
• Trypsin

Topics

• Body Fluids (enzymology)
• Bronchopulmonary Dysplasia (enzymology, etiology)
• Female
• Humans
• Infant
• Infant, Newborn
• Infant, Premature (metabolism)
• Male
• Pregnancy
• Suction
• Trachea
• Trypsin (analysis, biosynthesis, physiology)
• Trypsin Inhibitor, Kazal Pancreatic (immunology, metabolism)
• Trypsinogen (analysis)