Inflammatory stimuli recruit cathepsin activity to late endosomal compartments in human dendritic cells

Alfred Lautwein, Timo Burster, Ana-Maria Lennon-Duménil, Herman S Overkleeft, Ekkehard Weber, Hubert Kalbacher, Christoph Driessen

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Proteolysis by endocytic cysteine proteases is a central element of the antigen-presentation machinery in dendritic cells (DC). It controls the generation of immunogenic peptides, guides the transit of both MHC class II and MHC-like molecules through the endocytic compartment and converts class II into a peptide-receptive state - features closely linked to DC maturation. Differential activity of endocytic proteases, in particular cathepsins, in subcellular compartments has been implicated as a key regulatory element in controlling this machinery in murine DC. We analyzed the expression and subcellular distribution of the major endocytic cysteine proteases (cathepsins S, B, L and H) along with their major endogenous inhibitor, Cystatin C, in resting and stimulated human DC. Although the majority of cathepsin activity was restricted to lysosomes in resting DC, cathepsins selectively accumulated in late endosomes after LPS-induced stimulation. Surprisingly, expression and distribution of Cystatin C was unaffected by DC maturation. Thus, late endosomes represent a specialized compartment where proteolytic activity is developmentally regulated in DC. This could facilitate the conversion of exogenous protein into MHC class II-peptide complexes.

Original languageEnglish
Pages (from-to)3348-57
Number of pages10
JournalEuropean Journal of Immunology
Volume32
Issue number12
DOIs
Publication statusPublished - Dec 2002

Keywords

  • Cathepsins
  • Cell Differentiation
  • Cells, Cultured
  • Cystatin C
  • Cystatins
  • Dendritic Cells
  • Endosomes
  • Histocompatibility Antigens Class II
  • Humans
  • Hydrogen-Ion Concentration
  • Inflammation Mediators
  • Lipopolysaccharides
  • Receptors, IgG
  • Subcellular Fractions
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Inflammatory stimuli recruit cathepsin activity to late endosomal compartments in human dendritic cells'. Together they form a unique fingerprint.

Cite this