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Lysosomal cysteine proteases in the lung role in protein processing and immunoregulation..pdf

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Lysosomal cysteine proteases in the lung role in protein processing and immunoregulation.

REVIEW Lysosomal cysteine proteases in the lung: role in protein processing and immunoregulation F. Bu?hling*, N. Waldburg#, A. Reisenauer*, A. Heimburg*, H. Golpon#, T. Welte# Lysosomal cysteine proteases in the lung: role in protein processing and immuno- regulation. F. Bu?hling, N. Waldburg, A. Reisenauer, A. Heimburg, H. Golpon, T. Welte. #ERS Journals Ltd 2004. ABSTRACT: Lysosomal cysteine proteases are a family comprisingw10 enzymes. For many years it was believed that these enzymes catalyse protein breakdown unselectively, are highly redundant in their substrate specificity and are also expressed ubiquitously. This view has changed dramatically since a number of new lysosomal cysteine proteases with restricted expression and outstanding enzymatic activity have been described. In addition, knockout mice and selective protease inhibitors have been used to characterise specific functions of single proteases. In this review, some of these functions are discussed in relation to the lungs, especially the role of lysosomal cysteine proteases in matrix remodelling, immunoregulation and surfactant protein processing. Eur Respir J 2004; 23: 620–628. *Institute of Immunology, and #Dept of Pneumology and Critical Care, Otto-von- Guericke-University Magdeburg, Magdeburg, Germany. Correspondence: T. Welte, Dept of Pneumol- ogy and Critical Care, Otto-von-Guericke- University Magdeburg, Leipziger-Str. 44, 39120 Magdeburg, Germany. Fax: 49 39167190466 E-mail: tobias.welte@medizin.uni-magdeburg.de Keywords: Cathepsin, fibrosis, lung, protease, surfactant Received: September 16 2003 Accepted after revision: January 6 2004 Under normal conditions, up to 50% of proteins are degraded within the lysosomal compartment [1]. This finding, along with the short intralysosomal half-life of proteins, demonstrates the high activity of lysosomal proteases [2]. Lysosomal proteolysis is limited by the activity of endopro- teases that degrade internalised proteins into polypeptides. The termi