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Serglycin determine...
Serglycin determines secretory granule repertoire and regulates natural killer cell and cytotoxic T lymphocyte cytotoxicity
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- Sutton, Vivien R. (författare)
- Peter MacCallum Canc Ctr, Canc Cell Death Killer Cell Biol Labs, East Melbourne, Vic, Australia.
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- Brennan, Amelia J. (författare)
- Peter MacCallum Canc Ctr, Canc Cell Death Killer Cell Biol Labs, East Melbourne, Vic, Australia.
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- Ellis, Sarah (författare)
- Peter MacCallum Canc Ctr, Microscopy & Histol, East Melbourne, Vic, Australia.
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- Danne, Jill (författare)
- Peter MacCallum Canc Ctr, Microscopy & Histol, East Melbourne, Vic, Australia.
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- Thia, Kevin (författare)
- Peter MacCallum Canc Ctr, Canc Cell Death Killer Cell Biol Labs, East Melbourne, Vic, Australia.
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- Jenkins, Misty R. (författare)
- Peter MacCallum Canc Ctr, Canc Cell Death Killer Cell Biol Labs, East Melbourne, Vic, Australia.
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- Voskoboinik, Ilia (författare)
- Peter MacCallum Canc Ctr, Canc Cell Death Killer Cell Biol Labs, East Melbourne, Vic, Australia.
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- Pejler, Gunnar (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Uppsala University
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- Johnstone, Ricky W. (författare)
- Peter MacCallum Canc Ctr, Canc Cell Death Killer Cell Biol Labs, East Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3010, Australia.
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- Andrews, Daniel M. (författare)
- Peter MacCallum Canc Ctr, Canc Cell Death Killer Cell Biol Labs, East Melbourne, Vic, Australia.
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- Trapani, Joseph A. (författare)
- Peter MacCallum Canc Ctr, Canc Cell Death Killer Cell Biol Labs, East Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3010, Australia.
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Peter MacCallum Canc Ctr, Canc Cell Death Killer Cell Biol Labs, East Melbourne, Vic, Australia Peter MacCallum Canc Ctr, Microscopy & Histol, East Melbourne, Vic, Australia. (creator_code:org_t)
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- 2016-01-22
- 2016
- Engelska.
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 283:5, s. 947-961
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https://febs.onlinel...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://res.slu.se/i...
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Abstract
Ämnesord
Stäng
- The anionic proteoglycan serglycin is a major constituent of secretory granules in cytotoxic T lymphocyte (CTL)/natural killer (NK) cells, and is proposed to promote the safe storage of the mostly cationic granule toxins, granzymes and perforin. Despite the extensive defects of mast cell function reported in serglycin gene-disrupted mice, no comprehensive study of physiologically relevant CTL/NK cell populations has been reported. We show that the cytotoxicity of serglycin-deficient CTL and NK cells is severely compromised but can be partly compensated in both cell types when they become activated. Reduced intracellular granzyme B levels were noted, particularly in CD27(+)CD11b(+) mature NK cells, whereas serglycin(-/-) TCR-transgenic (OTI) CD8 T cells also had reduced perforin stores. Culture supernatants from serglycin(-/-) OTI T cells and interleukin-2-activated NK contained increased granzyme B, linking reduced storage with heightened export. By contrast, granzyme A was not significantly reduced in cells lacking serglycin, indicating differentially regulated trafficking and/or storage for the two granzymes. A quantitative analysis of different granule classes by transmission electronmicroscopy showed a selective loss of dense-core granules in serglycin(-/-) CD8(+) CTLs, although other granule types were maintained quantitatively. The findings of the present study show that serglycin plays a critical role in the maturation of dense-core cytotoxic granules in cytotoxic lymphocytes and the trafficking and storage of perforin and granzyme B, whereas granzyme A is unaffected. The skewed retention of cytotoxic effector molecules markedly reduces CTL/NK cell cytotoxicity, although this is partly compensated for as a result of activating the cells by physiological means.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- cytotoxic T lymphocyte
- granzymes
- natural killer cell
- perforin
- serglycin
Publikations- och innehållstyp
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Till lärosätets databas
- Av författaren/redakt...
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Sutton, Vivien R ...
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Brennan, Amelia ...
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Ellis, Sarah
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Danne, Jill
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Thia, Kevin
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Jenkins, Misty R ...
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visa fler...
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Voskoboinik, Ili ...
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Pejler, Gunnar
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Johnstone, Ricky ...
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Andrews, Daniel ...
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Trapani, Joseph ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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- Artiklar i publikationen
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The FEBS Journal
- Av lärosätet
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Uppsala universitet
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Sveriges Lantbruksuniversitet