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Cathepsin G enhances human natural killer cytotoxicity
Author(s) -
Tomomi Yamazaki,
Yosuke Aoki
Publication year - 1998
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1998.00397.x
Subject(s) - cytotoxicity , cathepsin g , cathepsin l1 , cathepsin , cathepsin c , microbiology and biotechnology , cathepsin l , natural killer cell , azurophilic granule , biology , cathepsin s , biochemistry , chemistry , proteases , in vitro , immunology , enzyme , myeloperoxidase , inflammation
Cathepsin G is a serine protease located in the azurophil granules of neutrophils. In this study, we investigated the effect of cathepsin G on the functions of human natural killer (NK) cells in vitro . Cathepsin G enhanced NK cytotoxicity rapidly in a dose‐dependent fashion. The ability to augment NK cytotoxicity was markedly reduced in the presence of the inhibitor, phenylmethanesulphonyl fluoride (PMSF) or chymostatin, demonstrating that the proteolytic activity of cathepsin G is essential for the induction of NK cytotoxicity. Granulocyte exocytosis is required for NK cell‐dependent target killing. Cathepsin G induced the release of the granule enzyme, N ‐acetyl‐β–glucosaminidase, from human NK cells. Moreover, an increase in the cytosolic‐free Ca 2+ concentration was observed in NK cells after stimulation with cathepsin G. When human granulocytes were stimulated with cytochalasin B and N ‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP), cathepsin G was released. The cathepsin G released from granulocytes also caused enhancement of NK cytotoxicity. In the presence of serine protease inhibitor the supernatant including cathepsin G obtained from stimulated granulocytes did not enhance NK cytotoxicity, but the stimulated granulocytes did. Highly purified human NK cells treated with cathepsin G enhanced NK cytotoxicity, but NK‐depleted lymphocytes did not, demonstrating that cathepsin G regulates NK cytotoxicity independently of other factors. We have shown recently that human cathepsin G binds to human NK cells. These combined data indicate that cathepsin G released from granulocytes binds to NK cells and augments NK cytotoxicity through its protease activity.