PROTECTION OF RAT LUNG FROM ELASTASE-INDUCED ELASTIC FIBER DEGRADATION IN-VITRO AND FROM EMPHYSEMA IN-VIVO BY A TRIFLUOROACETYLPEPTIDE ANILIDE INHIBITOR

Trifluoroacetylpeptide anilides are powerful reversible inhibitors of human neutrophil elastase (HNE), a serine protease implicated in the p athogenesis of pulmonary emphysema. The in vitro effectiveness of thre e inhibitors, CF3CO-Phe-Ala-NH-p-C6H4-CF3 (I), CF3CO-Val-Ala-NH-p-C6H4 -CF3 (2) and CF3CO-Lys-Ala-NH-p-C6H4-CH(CH3)(2) (3) was analyzed. The protection of lung tissue sections of rats from the degradation induce d by HNE has been evaluated quantitatively by automated image analysis . Inhibitor 1 (22 mu M), 2 (50 mu M) or 3 (35 and 70 mu M) significant ly reduced the HNE-induced degradation of the elastin network by 75, 4 2, 54 and 44%, respectively. Inhibitor 3 was tested intratracheally on an experimental model of pulmonary emphysema. Rats that received the elastase inhibitor 1 h before instillation of HNE were significantly p rotected by 40% from experimental emphysema. Reduced protections were observed with the treatment by the inhibitor 1 or 4 h after challenge with the enzyme.