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Granzyme B and natural killer (NK) cell death

  • REVIEW ARTICLE
  • Published:
Modern Rheumatology

Abstract

Granzyme B is a unique serine protease, which plays a crucial role for target cell death. Several mechanisms of delivery of granzyme B to target cells have been recently identified. Granzyme B directly activates Bid, a specific substrate for granzyme B, resulting in caspase activation. Granzyme B efficiently cleaves many prominent autoantigens, and the hypothesis that autoantibodies arise when cryptic determinants are revealed to the immune system has been proposed. Some autoantibodies directed against granzyme B-specific neoepitopes are present in serum from patients with autoimmune diseases. In the tissues from autoimmune diseases, granzyme B might play an important role for disease progression (i.e., rheumatoid arthritis synovium) or inhibition (i.e., regulatory T cells). We have identified a novel type of activation-induced cell death (granzyme B leakage-induced cell death). Activation-induced natural killer (NK) cell death is accompanied by the leakage of granzyme B from intracellular granules into the cytoplasm, and it triggers apoptosis by directing Bid to mitochondrial membranes. An excess of “leaked” granzyme B over its inhibitor, serpin proteinase inhibitor 9, is a major determinant of cell death. The role of granzyme B in autoimmunity and its influence on NK cell death are discussed.

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Authors and Affiliations

  1. First Department of Internal Medicine, Graduate School of Biochemical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Hiroaki Ida & Katsumi Eguchi

  2. Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

    Paul J. Utz

  3. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

    Paul Anderson

Authors
  1. Hiroaki Ida
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  2. Paul J. Utz
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  3. Paul Anderson
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  4. Katsumi Eguchi
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Correspondence to Hiroaki Ida.

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Ida, H., Utz, P., Anderson, P. et al. Granzyme B and natural killer (NK) cell death. Mod Rheumatol 15, 315–322 (2005). https://doi.org/10.1007/s10165-005-0426-6

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  • DOI: https://doi.org/10.1007/s10165-005-0426-6

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