SUSCEPTIBILITY OF LUNG EPITHELIUM TO NEUTROPHIL ELASTASE - PROTECTIONBY NATIVE INHIBITORS

The development of emphysema is thought to be due to an imbalance of p roteases (especially neutrophil elastase [NE]) and antiproteases with loosening of the respiratory epithelium as an early event. We investig ated the effect of NE on respiratory epithelial cell adherence in vitr o, in the presence of varying concentrations and combinations of nativ e inhibitors, alpha-1-proteinase inhibitor (PI) and secretory leukopro tease inhibitor (SLPI). SLPI was two to 12 times more effective than P I at preventing the effects of NE, especially when enzyme:inhibitor ra tios were almost equivalent, Even when the concentration of SLPI was o nly 10% of the total (as in normal peripheral lung secretions), it gav e greater protection than PI alone. This suggests that SLPI plays an i mportant role in controlling neutrophil elastase-induced inflammation and tissue damage.