Invariant chain controls the activity of extracellular cathepsin L

Fiebiger, E; Maehr, R; Villadangos, J; Weber, E; Erickson, A; Bikoff, E; Ploegh, HL; Lennon-Dumenil, AM

Author(s): Fiebiger, E; Maehr, R; Villadangos, J; Weber, E; Erickson, A; Bikoff, E; Ploegh, HL; Lennon-Dumenil, AM;
Details: Publication Year 2002-11-04,Volume 196,Issue #9,Page 1263-1269
Journal Title: JOURNAL OF EXPERIMENTAL MEDICINE
Publication Type: Journal Article
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 macrophages 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 p4165aa in culture supernatants from antigen-presenting cells (APCs). Extracellular accumulation of mature CatL is up-regulated by inflammatory stimuli as observed in interferon (IFN)-gamma-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.
Publisher: ROCKEFELLER UNIV PRESS
Keywords: LYSOSOMAL CYSTEINE PROTEASES; P41 ISOFORM; ANTIGEN PRESENTATION; DENDRITIC CELLS; L REVEALS; PROTEOLYSIS; MACROPHAGES; EXPRESSION; COMPLEX; CANCER
Publisher's Version: https://doi.org/10.1084/jem.20020762
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2002-11-04 12:00:00