ACTIVATION OF MMP-9 BY NEUTROPHIL ELASTASE IN AN IN-VIVO MODEL OF ACUTE LUNG INJURY

The effect of neutrophil elastase on the functional status of gelatina ses was studied in an hamster model developed by intratracheal adminis tration of lipopolysaccharide followed by in situ cell activation with phorbol myristate acetate. This resulted in the production in broncho alveolar lavage fluids, in addition to the matrix metalloproteinase MM P-9, of a 75 kDa gelatinase associated with collagenolytic activity. T reatment in vivo with an elastase inhibitor abolished the latter activ ity. Since, in addition, elastase activates in vitro purified MMP-9 ge latinase into a similar 75 kDa entity, these data suggest that elastas e maybe a physiological activator of MMP-9 in vivo.