PROTEINASE-ANTIPROTEINASE BALANCE IN TRACHEAL ASPIRATES FROM NEONATES

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 inj ury occurring due to inhibitory capacity being overwhelmed. Activities of neutrophil elastase and its inhibitors were measured in tracheal a spirates from 17 infants, 10 of whom subsequently developed bronchopul monary dysplasia. All aspirates contained immunologically detectable a lpha(1)-proteinase inhibitor (alpha(1)-PI), but their inhibitory capac ity against neutrophil elastase ranged from being undetectable to bein g in excess of the amount of alpha(1)-PI detected immunologically. Whe n the alpha(1)PI was removed from each of the aspirates, using a speci fic antibody, from 0-50% of the original activity remained, indicating the presence of another elastase inhibitor. Its properties were consi stent with it being the low molecular mass, secretory leucoproteinase inhibitor (SLPI), also known as bronchial antileucoproteinase. The alp ha(1)-PI was from 0-100% active. Most of the inactive inhibitor was sh own by western blotting to be complexed with elastase, with a small am ount of cleaved material There was no evidence of major oxidative inac tivation. Free elastase was detected in only three of the aspirates; t hese had little or no detectable elastase inhibitory capacity, and mos t of their alpha(1)-PI was complexed. Elastase load, comprising the su m of free and complexed elastase, correlated closely with myeloperoxid ase activity, a recognized marker of inflammatory activity. Active SLP I levels showed a positive correlation with gestational age (r=0.66). We conclude that most neutrophil elastase in the upper airways of vent ilated infants is complexed. This indicates that lung secretions of mo st infants contain adequate inhibitory activity of alpha(1)-PI and pro bably secretory leucoproteinase inhibitor.