The dual role of neutrophil elastase in lung destruction and repair.
The purpose of this review was to modify the prevailing view that neutrophil elastase (NE) is mainly a matrix-degrading enzyme. Recent observations indicate that the role of NE in inflammation is more complex than the simple degradation of extra-cellular matrix components. Several lines of evidence suggest that NE aims specifically at a variety of regulatory functions in local inflammatory processes. This enzyme can modulate many biological functions by promoting chemokine and cytokine activation and degradation, cytokine receptor shedding, proteolysis of cytokine binding proteins and the activation of different specific cell surface receptors. However, the current knowledge of regulatory mechanisms by which NE potentially regulates inflammatory processes is primarily derived from in vitro studies. The extent of these NE-dependent pathways and their relevance under various pathophysiological conditions remains poorly understood and a matter for further investigation. Recent studies suggest that NE not only plays a key role in lung destruction (emphysema) but can also modulate proliferative changes (fibrosis) in inflammatory processes. Thus, NE could be considered to have potential multiple roles in the pathogenesis of both emphysema and lung fibrosis.
Lungarella
Giuseppe
G
Department of Physiopathology and Experimental Medicine, University of Siena, via Aldo Moro n.6, I-53100 Siena, Italy. lungarella@unisi.it
Cavarra
Eleonora
E
Lucattelli
Monica
M
Martorana
Piero A
PA
D000818:Animals; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D019272:Leukocyte Elastase / Q000235:genetics / Q000378:metabolism*; D011656:Pulmonary Emphysema / Q000473:pathology* / Q000503:physiopathology*; D011658:Pulmonary Fibrosis / Q000473:pathology* / Q000503:physiopathology*
D016207:Cytokines; D019272:Leukocyte Elastase