Proteinase-antiproteinase bbalance in ttracheal aaspirates ffrom nneonates

We wanted to identify the inhibitors of neutrophil elastase, quantify their activities in the upper airways of neonates, and relate these to the presence of active elastase and the likelihood of elastolytic injury occurring due to inhibitory capacity being overwhelmed. Activities of neutrophil elastase and its inhibitors were measured in tracheal aspirates from 17 infants, 10 of whom subsequently developed bronchopulmonary dysplasia. All aspirates contained immunologically detectable α 1 -proteinase inhibitor (α 1 -PI), but their inhibitory capacity against neutrophil elastase ranged from being undetectable to being in excess of the amount of α 1 -PI detected immunologically. When the α 1 - PI was removed from each of the aspirates, using a specific antibody, from 0-50% of the original activity remained, indicating the presence of another elastase inhibitor. Its properties were consistent with it being the low molecular mass, secretory leucoproteinase inhibitor (SLPI), also known as bronchial antileucoproteinase. The α 1 -PI was from 0-100% active. Most of the inactive inhibitor was shown by western blotting to be complexed with elastase, with a small amount of cleaved material. There was no evidence of major oxidative inactivation. Free elastase was detected in only three of the aspirates; these had little or no detectable elastase inhibitory capacity, and most of their α 1 -PI was complexed. Elastase load, comprising the sum of free and complexed elastase, correlated closely with myeloperoxidase activity, a recognized marker of inflammatory activity. Active SLPI levels showed a positive correlation with gestational age (r=0.66). We conclude that most neutrophil elastase in the upper airways of ventilated infants is complexed. This indicates that lung secretions of most infants contain adequate inhibitory activity of α 1 -PI and probably secretory leucoproteinase inhibitor.