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*
Division of Immunology and Transplantation Biology, Department of Pediatrics, and Departments of
Cardiothoracic Surgery and
Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305;
Department of Pediatrics, University of California, San Francisco, CA 94143;
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Gwen Knapp Center for Lupus and Immunology Research, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637;
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Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121;
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Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213;
**
Evanston Northwestern Research Institute, Northwestern University, Evanston, IL 60201;
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104; and
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Department of Bioquimica, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain
Granulysin is an antimicrobial and tumoricidal molecule expressed
in granules of CTL and NK cells. In this study, we show that granulysin
damages cell membranes based upon negative charge, disrupts the
transmembrane potential (
) in mitochondria, and causes release of
cytochrome c. Granulysin-induced apoptosis is blocked in
cells overexpressing Bcl-2. Despite the release of cytochrome
c, procaspase 9 is not processed. Nevertheless,
activation of caspase 3 is observed in granulysin-treated cells,
suggesting that granulysin activates a novel pathway of CTL- and NK
cell-mediated death distinct from granzyme- and death receptor-induced
apoptosis.
This article has been cited by other articles:
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  H. Zhang, C. Zhong, L. Shi, Y. Guo, and Z. Fan Granulysin Induces Cathepsin B Release from Lysosomes of Target Tumor Cells to Attack Mitochondria through Processing of Bid Leading to Necroptosis J. Immunol., June 1, 2009; 182(11): 6993 - 7000. [Abstract] [Full Text] [PDF]
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 J. S. Mader, N. Mookherjee, R. E.W. Hancock, and R. C. Bleackley The Human Host Defense Peptide LL-37 Induces Apoptosis in a Calpain- and Apoptosis-Inducing Factor-Dependent Manner Involving Bax Activity Mol. Cancer Res., May 1, 2009; 7(5): 689 - 702. [Abstract] [Full Text] [PDF]
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 A. Nakashima, A. Shiozaki, S. Myojo, M. Ito, M. Tatematsu, M. Sakai, Y. Takamori, K. Ogawa, K. Nagata, and S. Saito Granulysin Produced by Uterine Natural Killer Cells Induces Apoptosis of Extravillous Trophoblasts in Spontaneous Abortion Am. J. Pathol., September 1, 2008; 173(3): 653 - 664. [Abstract] [Full Text] [PDF]
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L. P. Huang, S.-C. Lyu, C. Clayberger, and A. M. Krensky Granulysin-Mediated Tumor Rejection in Transgenic Mice J. Immunol., January 1, 2007; 178(1): 77 - 84. [Abstract] [Full Text] [PDF]
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 B. Liu, S. Liu, X. Qu, and J. Liu Construction of a eukaryotic expression system for granulysin and its protective effect in mice infected with Mycobacterium tuberculosis. J. Med. Microbiol., October 1, 2006; 55(Pt 10): 1389 - 1393. [Abstract] [Full Text] [PDF]
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A. Deng, S. Chen, Q. Li, S.-c. Lyu, C. Clayberger, and A. M. Krensky Granulysin, a Cytolytic Molecule, Is Also a Chemoattractant and Proinflammatory Activator J. Immunol., May 1, 2005; 174(9): 5243 - 5248. [Abstract] [Full Text] [PDF]
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 C. Dong, Q. Li, S.-c. Lyu, A. M. Krensky, and C. Clayberger A novel apoptosis pathway activated by the carboxyl terminus of p21 Blood, February 1, 2005; 105(3): 1187 - 1194. [Abstract] [Full Text] [PDF]
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 Q. Li, C. Dong, A. Deng, M. Katsumata, A. Nakadai, T. Kawada, S. Okada, C. Clayberger, and A. M. Krensky Hemolysis of Erythrocytes by Granulysin-Derived Peptides but Not by Granulysin Antimicrob. Agents Chemother., January 1, 2005; 49(1): 388 - 397. [Abstract] [Full Text] [PDF]
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L. L. Ma, C. L. C. Wang, G. G. Neely, S. Epelman, A. M. Krensky, and C. H. Mody NK Cells Use Perforin Rather than Granulysin for Anticryptococcal Activity J. Immunol., September 1, 2004; 173(5): 3357 - 3365. [Abstract] [Full Text] [PDF]
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S. Okada, Q. Li, J. C. Whitin, C. Clayberger, and A. M. Krensky Intracellular Mediators of Granulysin-Induced Cell Death J. Immunol., September 1, 2003; 171(5): 2556 - 2562. [Abstract] [Full Text] [PDF]
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A. Bose, Y. Inoue, K. E. Kokko, and F. G. Lakkis Cutting Edge: Perforin Down-Regulates CD4 and CD8 T Cell-Mediated Immune Responses to a Transplanted Organ J. Immunol., February 15, 2003; 170(4): 1611 - 1614. [Abstract] [Full Text] [PDF]
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L. L. Ma, J. C. L. Spurrell, J. F. Wang, G. G. Neely, S. Epelman, A. M. Krensky, and C. H. Mody CD8 T Cell-Mediated Killing of Cryptococcus neoformans Requires Granulysin and Is Dependent on CD4 T Cells and IL-15 J. Immunol., November 15, 2002; 169(10): 5787 - 5795. [Abstract] [Full Text] [PDF]
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Q. Sun, R. L. Burton, and K. G. Lucas Cytokine production and cytolytic mechanism of CD4+ cytotoxic T lymphocytes in ex vivo expanded therapeutic Epstein-Barr virus-specific T-cell cultures Blood, May 1, 2002; 99(9): 3302 - 3309. [Abstract] [Full Text] [PDF]
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J. Pardo, P. Perez-Galan, S. Gamen, I. Marzo, I. Monleon, A. A. Kaspar, S. A. Susin, G. Kroemer, A. M. Krensky, J. Naval, et al. A Role of the Mitochondrial Apoptosis-Inducing Factor in Granulysin-Induced Apoptosis J. Immunol., August 1, 2001; 167(3): 1222 - 1229. [Abstract] [Full Text] [PDF]
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