Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes / Jasmin Herz, Julian Pardo, Hamid Kashkar, Michael Schramm, Elza Kuzmenkina, Erik Bos, Katja Wiegmann, Reinhard Wallich, Peter J. Peters, Stefan Herzig, Elmon Schmelzer, Martin Krönke, Markus M. Simon & Olaf Utermöhlen
Granule-mediated cytotoxicity is the main effector mechanism of cytotoxic CD8+ T cells. We report that CD8+ T cells from acid sphingomyelinase (ASMase)-deficient (ASMase-KO) mice are defective in exocytosis of cytolytic effector molecules; this defect resulted in attenuated cytotoxic activity of ASMase-KO CD8+ T cells and delayed elimination of lymphocytic choriomeningitis virus from ASMase-KO mice. Cytolytic granules of ASMase-KO and wild-type CD8+ T cells were equally loaded with granzymes and perforin, and correctly directed to the immunological synapse. In wild-type CD8+ T cells, secretory granules underwent shrinkage by 82% after fusion with the plasma membrane. In ASMase-KO CD8+ T cells, the contraction of secretory granules was markedly impaired. Thus, ASMase is required for contraction of secretory granules and expulsion of cytotoxic effector molecules..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
14 June 2009 2009 |
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| Erschienen: |
14 June 2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Nature immunology - 10(2009), 7, Seite 761-768 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Herz, Jasmin, 1979- [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Gesehen am 17.05.2021 |
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| Umfang: |
8 |
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| doi: |
10.1038/ni.1757 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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1757914919 |
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| 245 | 1 | 0 | |a Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes |c Jasmin Herz, Julian Pardo, Hamid Kashkar, Michael Schramm, Elza Kuzmenkina, Erik Bos, Katja Wiegmann, Reinhard Wallich, Peter J. Peters, Stefan Herzig, Elmon Schmelzer, Martin Krönke, Markus M. Simon & Olaf Utermöhlen |
| 264 | 1 | |c 14 June 2009 | |
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| 500 | |a Gesehen am 17.05.2021 | ||
| 520 | |a Granule-mediated cytotoxicity is the main effector mechanism of cytotoxic CD8+ T cells. We report that CD8+ T cells from acid sphingomyelinase (ASMase)-deficient (ASMase-KO) mice are defective in exocytosis of cytolytic effector molecules; this defect resulted in attenuated cytotoxic activity of ASMase-KO CD8+ T cells and delayed elimination of lymphocytic choriomeningitis virus from ASMase-KO mice. Cytolytic granules of ASMase-KO and wild-type CD8+ T cells were equally loaded with granzymes and perforin, and correctly directed to the immunological synapse. In wild-type CD8+ T cells, secretory granules underwent shrinkage by 82% after fusion with the plasma membrane. In ASMase-KO CD8+ T cells, the contraction of secretory granules was markedly impaired. Thus, ASMase is required for contraction of secretory granules and expulsion of cytotoxic effector molecules. | ||
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Arenaviridae Infections | |
| 650 | 4 | |a CD8-Positive T-Lymphocytes | |
| 650 | 4 | |a Chemokine CCL5 | |
| 650 | 4 | |a Cytotoxicity, Immunologic | |
| 650 | 4 | |a Female | |
| 650 | 4 | |a Granzymes | |
| 650 | 4 | |a Immunoblotting | |
| 650 | 4 | |a Immunological Synapses | |
| 650 | 4 | |a Lymphocytic choriomeningitis virus | |
| 650 | 4 | |a Male | |
| 650 | 4 | |a Mice | |
| 650 | 4 | |a Mice, Knockout | |
| 650 | 4 | |a Microscopy, Fluorescence | |
| 650 | 4 | |a Perforin | |
| 650 | 4 | |a Reverse Transcriptase Polymerase Chain Reaction | |
| 650 | 4 | |a Secretory Vesicles | |
| 650 | 4 | |a Sphingomyelin Phosphodiesterase | |
| 650 | 4 | |a T-Lymphocytes | |
| 650 | 4 | |a T-Lymphocytes, Cytotoxic | |
| 700 | 1 | |a Pardo, Julian |e verfasserin |4 aut | |
| 700 | 1 | |a Kashkar, Hamid |e verfasserin |4 aut | |
| 700 | 1 | |a Schramm, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Kuzmenkina, Elza |e verfasserin |4 aut | |
| 700 | 1 | |a Bos, Erik |e verfasserin |4 aut | |
| 700 | 1 | |a Wiegmann, Katja |e verfasserin |4 aut | |
| 700 | 1 | |a Wallich, Reinhard |e verfasserin |0 (DE-588)1059566710 |0 (DE-627)798640839 |0 (DE-576)163467781 |4 aut | |
| 700 | 1 | |a Peters, Peter J. |e verfasserin |4 aut | |
| 700 | 1 | |a Herzig, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Schmelzer, Elmon |e verfasserin |4 aut | |
| 700 | 1 | |a Krönke, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Simon, Markus M. |e verfasserin |4 aut | |
| 700 | 1 | |a Utermöhlen, Olaf |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:10 |g year:2009 |g number:7 |g pages:761-768 |g extent:8 |
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| 856 | 4 | 0 | |u https://www.nature.com/articles/ni.1757 |x Verlag |z lizenzpflichtig |3 Volltext |
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| 912 | |a GBV_ILN_206 | ||
| 912 | |a GBV_ILN_213 | ||
| 912 | |a GBV_ILN_224 | ||
| 912 | |a GBV_ILN_230 | ||
| 912 | |a GBV_ILN_285 | ||
| 912 | |a GBV_ILN_293 | ||
| 912 | |a GBV_ILN_370 | ||
| 912 | |a GBV_ILN_374 | ||
| 912 | |a GBV_ILN_602 | ||
| 912 | |a GBV_ILN_603 | ||
| 912 | |a GBV_ILN_647 | ||
| 912 | |a GBV_ILN_702 | ||
| 912 | |a GBV_ILN_2001 | ||
| 912 | |a GBV_ILN_2003 | ||
| 912 | |a GBV_ILN_2004 | ||
| 912 | |a GBV_ILN_2005 | ||
| 912 | |a GBV_ILN_2006 | ||
| 912 | |a GBV_ILN_2007 | ||
| 912 | |a GBV_ILN_2008 | ||
| 912 | |a GBV_ILN_2009 | ||
| 912 | |a GBV_ILN_2010 | ||
| 912 | |a GBV_ILN_2011 | ||
| 912 | |a GBV_ILN_2014 | ||
| 912 | |a GBV_ILN_2015 | ||
| 912 | |a GBV_ILN_2018 | ||
| 912 | |a GBV_ILN_2020 | ||
| 912 | |a GBV_ILN_2021 | ||
| 912 | |a GBV_ILN_2025 | ||
| 912 | |a GBV_ILN_2026 | ||
| 912 | |a GBV_ILN_2027 | ||
| 912 | |a GBV_ILN_2031 | ||
| 912 | |a GBV_ILN_2034 | ||
| 912 | |a GBV_ILN_2037 | ||
| 912 | |a GBV_ILN_2038 | ||
| 912 | |a GBV_ILN_2043 | ||
| 912 | |a GBV_ILN_2044 | ||
| 912 | |a GBV_ILN_2048 | ||
| 912 | |a GBV_ILN_2050 | ||
| 912 | |a GBV_ILN_2055 | ||
| 912 | |a GBV_ILN_2056 | ||
| 912 | |a GBV_ILN_2057 | ||
| 912 | |a GBV_ILN_2059 | ||
| 912 | |a GBV_ILN_2061 | ||
| 912 | |a GBV_ILN_2064 | ||
| 912 | |a GBV_ILN_2068 | ||
| 912 | |a GBV_ILN_2088 | ||
| 912 | |a GBV_ILN_2093 | ||
| 912 | |a GBV_ILN_2108 | ||
| 912 | |a GBV_ILN_2110 | ||
| 912 | |a GBV_ILN_2111 | ||
| 912 | |a GBV_ILN_2112 | ||
| 912 | |a GBV_ILN_2113 | ||
| 912 | |a GBV_ILN_2116 | ||
| 912 | |a GBV_ILN_2118 | ||
| 912 | |a GBV_ILN_2119 | ||
| 912 | |a GBV_ILN_2129 | ||
| 912 | |a GBV_ILN_2143 | ||
| 912 | |a GBV_ILN_2147 | ||
| 912 | |a GBV_ILN_2148 | ||
| 912 | |a GBV_ILN_2152 | ||
| 912 | |a GBV_ILN_2153 | ||
| 912 | |a GBV_ILN_2158 | ||
| 912 | |a GBV_ILN_2190 | ||
| 912 | |a GBV_ILN_2193 | ||
| 912 | |a GBV_ILN_2336 | ||
| 912 | |a GBV_ILN_2472 | ||
| 912 | |a GBV_ILN_2522 | ||
| 912 | |a GBV_ILN_2911 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4035 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4046 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4125 | ||
| 912 | |a GBV_ILN_4126 | ||
| 912 | |a GBV_ILN_4242 | ||
| 912 | |a GBV_ILN_4246 | ||
| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4251 | ||
| 912 | |a GBV_ILN_4277 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4307 | ||
| 912 | |a GBV_ILN_4313 | ||
| 912 | |a GBV_ILN_4322 | ||
| 912 | |a GBV_ILN_4323 | ||
| 912 | |a GBV_ILN_4324 | ||
| 912 | |a GBV_ILN_4325 | ||
| 912 | |a GBV_ILN_4326 | ||
| 912 | |a GBV_ILN_4328 | ||
| 912 | |a GBV_ILN_4333 | ||
| 912 | |a GBV_ILN_4336 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4346 | ||
| 912 | |a GBV_ILN_4367 | ||
| 912 | |a GBV_ILN_4393 | ||
| 912 | |a GBV_ILN_4700 | ||
| 912 | |a GBV_ILN_4753 | ||
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