Metalloproteinase-mediated release of human Fas ligand

doi:10.1084/jem.182.6.1777

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Metalloproteinase-mediated release of human Fas ligand

N Kayagaki, A Kawasaki, T Ebata, H Ohmoto, S Ikeda, S Inoue, K Yoshino, K Okumura and H Yagita
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.

Fas ligand (FasL) is a type II integral membrane protein homologous with tumor necrosis factor (TNF). Recent studies indicate that TNF is processed to yield the soluble cytokine by metalloproteinases at the cell surface of activated macrophages and T cells. In the present study, we investigated whether FasL is also released by metalloproteinases. Treatment with hydroxamic acid inhibitors of matrix metalloproteinases specifically led to accumulation of membrane-type FasL (p40) on the surface of human FasL cDNA transfectants and activated human T cells, as estimated by surface immunofluorescence and immunoprecipitation with newly established anti-human FasL monoclonal antibodies. This surface accumulation of mFasL was associated with the decrease of soluble FasL (p27) in the supernatant as estimated by quantitative ELISA and immunoprecipitation with anti-human FasL monoclonal antibodies. These results indicate that human FasL is efficiently released from the cell surface by metalloproteinases like TNF.
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Yu, Y., Hagihara, M., Ando, K., Gansuvd, B., Matsuzawa, H., Tsuchiya, T., Ueda, Y., Inoue, H., Hotta, T., Kato, S. (2001). Enhancement of Human Cord Blood CD34+ Cell-Derived NK Cell Cytotoxicity by Dendritic Cells. J. Immunol. 166: 1590-1600 [Abstract] [Full Text]
Wei, C.-H., Yagita, H., Masucci, M. G., Levitsky, V. (2001). Different Programs of Activation-Induced Cell Death Are Triggered in Mature Activated CTL by Immunogenic and Partially Agonistic Peptide Ligands. J. Immunol. 166: 989-995 [Abstract] [Full Text]
Ahmad, R., Menezes, J., Knafo, L., Ahmad, A. (2001). Activated human platelets express Fas-L and induce apoptosis in Fas-positive tumor cells. J. Leukoc. Biol. 69: 123-128 [Abstract] [Full Text]
Mitsiades, N., Yu, W.-h., Poulaki, V., Tsokos, M., Stamenkovic, I. (2001). Matrix Metalloproteinase-7-mediated Cleavage of Fas Ligand Protects Tumor Cells from Chemotherapeutic Drug Cytotoxicity. Cancer Res. 61: 577-581 [Abstract] [Full Text]
Klasa, R. J., List, A. F., Cheson, B. D. (2001). Rational Approaches to Design of Therapeutics Targeting Molecular Markers. ASH Education Book 2001: 443-462 [Abstract] [Full Text]
Jodo, S., Hohlbaum, A. M., Xiao, S., Chan, D., Strehlow, D., Sherr, D. H., Marshak-Rothstein, A., Ju, S.-T. (2000). CD95 (Fas) Ligand-Expressing Vesicles Display Antibody-Mediated, FcR-Dependent Enhancement of Cytotoxicity. J. Immunol. 165: 5487-5494 [Abstract] [Full Text]
Waku, T., Fujiwara, T., Shao, J., Itoshima, T., Murakami, T., Kataoka, M., Gomi, S., Roth, J. A., Tanaka, N. (2000). Contribution of CD95 Ligand-Induced Neutrophil Infiltration to the Bystander Effect in p53 Gene Therapy for Human Cancer. J. Immunol. 165: 5884-5890 [Abstract] [Full Text]
Nakayama, M., Kayagaki, N., Yamaguchi, N., Okumura, K., Yagita, H. (2000). Involvement of TWEAK in Interferon {gamma}-stimulated Monocyte Cytotoxicity. J. Exp. Med. 192: 1373-1380 [Abstract] [Full Text]
Sampalo, A., Navas, G., Medina, F., Segundo, C., Camara, C., Brieva, J. A. (2000). Chronic lymphocytic leukemia B cells inhibit spontaneous Ig production by autologous bone marrow cells: role of CD95-CD95L interaction. Blood 96: 3168-3174 [Abstract] [Full Text]
Morel, Y., Schiano de Colella, J.-M., Harrop, J., Deen, K. C., Holmes, S. D., Wattam, T. A., Khandekar, S. S., Truneh, A., Sweet, R. W., Gastaut, J.-A., Olive, D., Costello, R. T. (2000). Reciprocal Expression of the TNF Family Receptor Herpes Virus Entry Mediator and Its Ligand LIGHT on Activated T Cells: LIGHT Down-Regulates Its Own Receptor. J. Immunol. 165: 4397-4404 [Abstract] [Full Text]
Kahl, S., Nissen, M., Girisch, R., Duffy, T., Leiter, E. H., Haag, F., Koch-Nolte, F. (2000). Metalloprotease-Mediated Shedding of Enzymatically Active Mouse ecto-ADP-ribosyltransferase ART2.2 Upon T Cell Activation. J. Immunol. 165: 4463-4469 [Abstract] [Full Text]
Sugita, S., Taguchi, C., Takase, H., Sagawa, K., Sueda, J., Fukushi, K., Hikita, N., Watanabe, T., Itoh, K., Mochizuki, M. (2000). Soluble Fas ligand and soluble Fas in ocular fluid of patients with uveitis. Br. J. Ophthalmol. 84: 1130-1134 [Abstract] [Full Text]
Imanishi, T., Murry, C. E., Reinecke, H., Hano, T., Nishio, I., Liles, W.C., Hofsta, L., Kim, K., O'Brien, K. D., Schwartz, S. M., Han, D. K.M. (2000). Cellular FLIP is expressed in cardiomyocytes and down-regulated in TUNEL-positive grafted cardiac tissues. Cardiovasc Res 48: 101-110 [Abstract] [Full Text]
Brandau, S., Suttmann, H., Riemensberger, J., Seitzer, U., Arnold, J., Durek, C., Jocham, D., Flad, H.-D., Böhle, A. (2000). Perforin-mediated Lysis of Tumor Cells by Mycobacterium Bovis Bacillus Calmette-Guerin-activated Killer Cells. Clin. Cancer Res. 6: 3729-3738 [Abstract] [Full Text]
Jeremias, I., Kupatt, C., Martin-Villalba, A., Habazettl, H., Schenkel, J., Boekstegers, P., Debatin, K. M. (2000). Involvement of CD95/Apo1/Fas in Cell Death After Myocardial Ischemia. Circulation 102: 915-920 [Abstract] [Full Text]
Dri, P., Gasparini, C., Menegazzi, R., Cramer, R., Alberi, L., Presani, G., Garbisa, S., Patriarca, P. (2000). TNF-Induced Shedding of TNF Receptors in Human Polymorphonuclear Leukocytes: Role of the 55-kDa TNF Receptor and Involvement of a Membrane-Bound and Non-Matrix Metalloproteinase. J. Immunol. 165: 2165-2172 [Abstract] [Full Text]