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Invariant Chain Controls the Activity of Extracellular Cathepsin L

Invariant Chain Controls the Activity of Extracellular Cathepsin L Secretion of proteases is critical for degradation of the extracellular matrix during an inflammatory response. Cathepsin (Cat) S and L are the major elastinolytic cysteine proteases in mouse macrophages. A 65 amino acid segment of the p41 splice variant (p41 65aa ) of major histocompatibility complex class II–associated invariant chain (Ii) binds to the active site of CatL and permits the maintenance of a pool of mature enzyme in endosomal compartments of macro-phages and dendritic cells (DCs). Here we show that interaction of p41 65aa with mature CatL allows extracellular accumulation of the active enzyme. We detected mature CatL as a complex with p41 65aa in culture supernatants from antigen-presenting cells (APCs). Extracellular accumulation of mature CatL is up-regulated by inflammatory stimuli as observed in interferon (IFN)-γ–treated macrophages and lipopolysaccharide (LPS)-activated DCs. Despite the neutral pH of the extracellular milieu, released CatL associated with p41 65aa is catalytically active as demonstrated by active site labeling and elastin degradation assays. We propose that p41 65aa stabilizes CatL in the extracellular environment and induces a local increase in the concentration of matrix-degrading enzymes during inflammation. Through its interaction with CatL, Ii may therefore control the migratory response of APCs and/or the recruitment of effectors of the inflammatory response. protease invariant chain secretion antigen-presenting cells extracellular matrix degradation Footnotes Submitted: 10 May 2002 Accepted: 1 October 2002 Revision received 25 September 2002 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Experimental Medicine Rockefeller University Press

Invariant Chain Controls the Activity of Extracellular Cathepsin L

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Publisher
Rockefeller University Press
Copyright
© 2002 Rockefeller University Press
ISSN
0022-1007
eISSN
1540-9538
DOI
10.1084/jem.20020762
Publisher site
See Article on Publisher Site

Abstract

Secretion of proteases is critical for degradation of the extracellular matrix during an inflammatory response. Cathepsin (Cat) S and L are the major elastinolytic cysteine proteases in mouse macrophages. A 65 amino acid segment of the p41 splice variant (p41 65aa ) of major histocompatibility complex class II–associated invariant chain (Ii) binds to the active site of CatL and permits the maintenance of a pool of mature enzyme in endosomal compartments of macro-phages and dendritic cells (DCs). Here we show that interaction of p41 65aa with mature CatL allows extracellular accumulation of the active enzyme. We detected mature CatL as a complex with p41 65aa in culture supernatants from antigen-presenting cells (APCs). Extracellular accumulation of mature CatL is up-regulated by inflammatory stimuli as observed in interferon (IFN)-γ–treated macrophages and lipopolysaccharide (LPS)-activated DCs. Despite the neutral pH of the extracellular milieu, released CatL associated with p41 65aa is catalytically active as demonstrated by active site labeling and elastin degradation assays. We propose that p41 65aa stabilizes CatL in the extracellular environment and induces a local increase in the concentration of matrix-degrading enzymes during inflammation. Through its interaction with CatL, Ii may therefore control the migratory response of APCs and/or the recruitment of effectors of the inflammatory response. protease invariant chain secretion antigen-presenting cells extracellular matrix degradation Footnotes Submitted: 10 May 2002 Accepted: 1 October 2002 Revision received 25 September 2002

Journal

The Journal of Experimental Medicine – Rockefeller University Press

Published: Nov 4, 2002

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