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Inhibitors of elastase in airway lavage samples from ventilated preterm human neonates
Insights
Neonatal lung injury involves elastase activity primarily in cells, with acid-resistant inhibitors playing a key role. Their functional activity decreases in soluble fractions during infection, highlighting the need for comprehensive assessment.
Area of Science:
- Pulmonary Medicine
- Neonatology
- Biochemistry
Background:
- Neutrophil elastase is implicated in lung injury.
- Alpha1-protease inhibitor (alpha1-PI) and acid-resistant inhibitors (mucus protease inhibitor [MPI] and elastase-specific inhibitor [ESI/Elafin]) balance elastase.
- The role of these inhibitors in neonates is not well-defined.
Purpose of the Study:
- To characterize the functional role of acid-resistant protease inhibitors in neonatal lung injury.
- To investigate the distribution and activity of elastase and its inhibitors in cellular and soluble fractions of neonatal airway lavage fluid.
- To assess changes in inhibitor activity during nosocomial infection in mechanically ventilated neonates.
Main Methods:
- Analysis of saline airway lavage samples from intubated neonates.
- Separation of samples into cellular and soluble fractions via centrifugation.
- Quantification of elastase activity and functional activity of alpha1-PI, MPI, and ESI/Elafin.
Main Results:
- During the first 36 hours of life, elastase activity was mainly cellular.
- Acid-resistant inhibitors were significantly cell-associated, while alpha1-PI was not.
- In the soluble fraction, acid-resistant inhibitors showed limited functional activity compared to alpha1-PI.
- In infected neonates, functional activity of soluble acid-resistant inhibitors decreased, despite unchanged total mass.
Conclusions:
- Neonatal lung injury involves a distinct compartmentalization of elastase activity and protease inhibitors.
- Acid-resistant inhibitors are crucial in the cellular compartment in neonates.
- Reduced functional activity of soluble acid-resistant inhibitors may indicate impaired protease-antiprotease balance during infection.
- Comprehensive assessment requires evaluating both cellular and soluble lavage compartments.
Abstract:
Surplus elastase released from neutrophils during lung injury is balanced mainly by alpha1-protease inhibitor (alpha1-PI) and by two acid-resistant inhibitors. The latter include mucus protease inhibitor (MPI, also named SLPI, BSI, ALP) and elastase-specific inhibitor (ESI or Elafin), but their functional role during the neonatal period has not yet been characterized precisely. The saline airway lavage samples from neonates intubated for respiratory distress were separated by centrifugation into a cellular and a soluble, supernatant fraction and then analyzed. During the first 36 h of life (42 neonates, gestational age 24-40 wk), elastase activity was confined to the cellular fraction. Thirty percent of the acid-resistant inhibitors but almost no alpha1-PI, was cell-associated. In the soluble fraction, about 20-30% of the acid-resistant inhibitors was functionally active, but only about 10% of alpha1-PI was. In seven infants with a nosocomial infection and deterioration during mechanical ventilation, only a very modest increase in elastase activity was observed. However, the functional activity of the acid-resistant inhibitors was reduced in the soluble fraction, whereas total mass remained unchanged. A full assessment of protease and protease inhibitors should include the cellular and the soluble lavage compartments.