Gamma‐interferon causes a selective induction of the lysosomal proteases, cathepsins B and L, in macrophages
- 17 April 1995
- journal article
- Published by Wiley in FEBS Letters
- Vol. 363 (1-2) , 85-89
- https://doi.org/10.1016/0014-5793(95)00287-j
Abstract
Previous studies have indicated that acid-optimal cysteine proteinase(s) in the endosomal-lysosomal compartments, cathepsins, play a critical role in the proteolytic processing of endocytosed proteins to generate the antigenic peptides presented to the immune system on major histocompatibility complex (MHC) class II molecules. The presentation of these peptides and the expression of MHC class II molecules by macrophages and lymphocytes are stimulated by γ-interferon (γ-IFN). We found that treatment of human U-937 monocytes with γ-IFN increased the activities and the content of the two major lysosomal cysteine proteinases, cathepsins B and L. Assays of protease activity, enzyme-linked immunosorbant assays (ELISA) and immunoblotting showed that this cytokine increased the amount of cathepsin B 5-fold and cathepsin L 3-fold in the lysosomal fraction. By contrast, the aspartic proteinase, cathepsin D, in this fraction was not significantly altered by γ-IFN treatment. An induction of cathepsins B and L was also observed in mouse macrophages, but not in HeLa cells. These results suggest coordinate regulation in monocytes of the expression of cathepsins B and L and MHC class II molecules. Presumably, this induction of cysteine proteases contributes to the enhancement of antigen presentation by γ-IFNKeywords
This publication has 30 references indexed in Scilit:
- Immunological significances of invariant chain from the aspect of its structural homology with the cystatin familyFEBS Letters, 1994
- Regulation of MHC Class II Expression by Interferon-γ Mediated by the Transactivator Gene CIITAScience, 1994
- Isolation and characterization of the intracellular MHC class II compartmentNature, 1994
- MHC-dependent antigen processing and peptide presentation: Providing ligands for T lymphocyte activationCell, 1994
- Purification of the complex of cathepsin L and the MHC class II‐associated invariant chain fragment from human kidneyFEBS Letters, 1993
- Major involvement of cathepsin B in the intracellular proteolytic processing of exogenous IgGs in U937 cellsMolecular Immunology, 1993
- Participation of cathepsin B in processing of antigen presentation to MHC class IIFEBS Letters, 1993
- Evidence supporting a role for cathepsin B in the generation of T cell antigenic epitopes of human growth hormoneMolecular Immunology, 1993
- Novel epoxysuccinyl peptides A selective inhibitor of cathepsin B, in vivoFEBS Letters, 1991
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976