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Blood, 15 July 2007, Vol. 110, No. 2, pp. 544-552. Prepublished online as a Blood First Edition Paper on April 4, 2007; DOI 10.1182/blood-2006-10-051649. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2006-10-051649v1 110/2/544    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fellows, E. Articles by Kurschus, F. C. Search for Related Content PubMed PubMed Citation Articles by Fellows, E. Articles by Kurschus, F. C. Related Collections Apoptosis Free Research Articles Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Natural killer cell–derived human granzyme H induces an alternative, caspase-independent cell-death program Edward Fellows1, Shirley Gil-Parrado2, Dieter E. Jenne1, and Florian C. Kurschus1 1 Department of Neuroimmunology, Max-Planck-Institut of Neurobiology, Martinsried, Germany; and 2 Abteilung für Klinische Chemie und Klinische Biochemie, Chirurgische Klinik Innenstadt, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany Granzyme H (GzmH) belongs to a family of 5 human serine proteases that are expressed by cytotoxic immune effector cells. Although GzmH is most closely related to the caspase-activating granzyme B (GzmB), neither a natural substrate nor a role in immune defense reactions has been demonstrated for this orphan granzyme. In rodents, multiple related genes exist, but none of these can be regarded as functional homologs. Here we show that host cells are efficiently killed by GzmH after perforin and streptolysin O–mediated delivery into the cytosol. Dying cells show typical hallmarks of programmed cell death, such as mitochondrial depolarization, reactive oxygen species (ROS) generation, DNA degradation, and chromatin condensation. Contrary to GzmB, cell death by GzmH does not involve the activation of executioner caspases, the cleavage of Bid or inhibitor of caspase-activated DNase (ICAD), or the release of cytochrome c. The high expression levels of GzmH in naive natural killer (NK) cells and its potent killing ability strongly support the role of the protease in triggering an alternative cell-death pathway in innate immunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Orphan granzyme turned lethal weapon Todd A. Fehniger Blood 2007 110: 475-476. [Full Text] [PDF] This article has been cited by other articles: T. Connerotte, A. Van Pel, D. Godelaine, E. Tartour, B. Schuler-Thurner, S. Lucas, K. Thielemans, G. Schuler, and P. G. Coulie Functions of Anti-MAGE T-Cells Induced in Melanoma Patients under Different Vaccination Modalities Cancer Res., May 15, 2008; 68(10): 3931 - 3940. [Abstract] [Full Text] [PDF]

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