EPITHELIAL-CELL DAMAGE IS INDUCED BY NEUTROPHIL-DERIVED, NOT PSEUDOMONAS-DERIVED, PROTEASES IN CYSTIC-FIBROSIS SPUTUM

Airway histopathological changes in cystic fibrosis (CF) include damag e to the epithelial tissue and accumulation of polymorphonuclear leuko cytes (PMN). Airways of CF patients are usually colonized with bacteri a such as mucoid Pseudomonas aeruginosa (PA). Bacteria and PMN can bot h release proteolytic enzymes capable of causing tissue damage. This s tudy aims to clarify and compare the roles of these agents in epitheli um damage. Epithelial cell (EC) damage and detachment induced by sputu m samples from CF or non-CF patients, with and without lung infection, were assessed on amnionic EC in an in vitro model of airway epitheliu m. Protease activity was determined using inhibitor profiles, and comp ared to the proteolytic activity of isolated neutrophils and bacteria. Sputa from CF patients and infected non-CF patients induced high leve ls of detachment. PA also induced high levels of EC detachment but Sta phylococcus aureus and Haemophilus influenzae, two other bacteria comm only isolated from CF sputa, induced no detachment. Antiprotease inhib ition profiles were similar for PMN and sputa-induced EC detachment, b ut different for PA-induced detachment. These results suggest that PMN proteolytic enzymes, probably elastase and cathepsin G, are more like ly to be the inducers of tissue damage in the airways of CF patients t han PA proteolytic enzymes.