Gamma-interferon causes a selective induction of the lysosomal proteases, cathepsins B and L, in macrophages.
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 gamma-interferon (gamma-IFN). We found that treatment of human U-937 monocytes with gamma-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 gamma-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 gamma-IFN.
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Albert Einstein Medical Center, Department of Pathology and Laboratory of Medicine, Philadelphia, PA 19141, USA.
Hawley
M
M
Rock
K L
KL
Goldberg
A L
AL
D000818:Animals; D002401:Cathepsin B / Q000096:biosynthesis*; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis*; D002460:Cell Line; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D006367:HeLa Cells / Q000201:enzymology; D006801:Humans; D015151:Immunoblotting; D007371:Interferon-gamma / Q000494:pharmacology*; D008247:Lysosomes / Q000201:enzymology*; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D009000:Monocytes / Q000201:enzymology; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D007371:Interferon-gamma; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse