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Sorting soluble tumor necrosis factor (TNF) receptor for storage and regulated secretion in hematopoietic cells.
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- Gao, Ying (författare)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine
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- Hansson, Markus (författare)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine
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Calafat, Jero (författare)
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- Tapper, Hans (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Olsson, Inge (författare)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine
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(creator_code:org_t)
- 2004-07-07
- 2004
- Engelska.
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Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 76:4, s. 876-885
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://jlb.onlineli...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Hematopoietic cells contain secretory lysosomes that degranulate at sites of inflammation. We envisage that secretory granules can act as vehicles for targeting inflammatory sites, including malignancies, and thereafter, locally release therapeutically active agents to these sites. Exogenous proteins, such as the soluble tumor necrosis factor receptor 1 (sTNFR1), have been shown previously to be targeted to secretory lysosomes [1]. In this work, we asked whether exogenons, secretory lysosome-targeted proteins were subject to regulated secretion. sTNFR1-transmembrane (tm)cytosol-sorting signal (Y) and sTNFR1-tm-Y-enhanced green fluorescent protein (egfp) were expressed in rat basophilic leukemia cell clones having different secretory capacities. sTNFR1-tm-Y was targeted directly from the Golgi to secretory lysosomes, followed by generation of membrane-free sTNFR1, whose secretion could be triggered by a Ca2+ ionophore or inummoglobulin E receptor activation. In contrast, sTNFRI-tm-Y-egfp was targeted to the plasma membrane and then subjected to endocytosis and presumably, secretory lysosome targeting, as judged by results from antibody ligation and cell-surface biotinylation. Activation of protein kinase C with phorbol ester promoted ectodomain shedding at the cell surface, resulting in sTNFR1 release from sTNFR1-tm-Y-egfp. These results support a concept for using the storage organelles of hematopoietic cells as vehicles for targeting sites of inflammation with therapeutically active agents.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- secretary lysosome
- endosome pathway
- inflammation
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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