Inhibitors of elastase in airway lavage samples from ventilated preterm human neonates

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.