Sorting soluble tumor necrosis factor (TNF) receptor for storage and regulated secretion in hematopoietic cells.
(2004) In Journal of Leukocyte Biology 76(4). p.876-885- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/125929
- author
- Gao, Ying LU ; Hansson, Markus LU ; Calafat, Jero ; Tapper, Hans LU and Olsson, Inge LU
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- secretary lysosome, endosome pathway, inflammation
- in
- Journal of Leukocyte Biology
- volume
- 76
- issue
- 4
- pages
- 876 - 885
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000224183100015
- scopus:4744359700
- ISSN
- 1938-3673
- DOI
- 10.1189/jlb.1103593
- language
- English
- LU publication?
- yes
- id
- 7286ab52-b431-4ffd-8907-c648f5cea6b1 (old id 125929)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15240756&dopt=Abstract
- date added to LUP
- 2016-04-01 11:42:41
- date last changed
- 2022-01-26 17:06:29
@article{7286ab52-b431-4ffd-8907-c648f5cea6b1, abstract = {{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.}}, author = {{Gao, Ying and Hansson, Markus and Calafat, Jero and Tapper, Hans and Olsson, Inge}}, issn = {{1938-3673}}, keywords = {{secretary lysosome; endosome pathway; inflammation}}, language = {{eng}}, number = {{4}}, pages = {{876--885}}, publisher = {{John Wiley & Sons Inc.}}, series = {{Journal of Leukocyte Biology}}, title = {{Sorting soluble tumor necrosis factor (TNF) receptor for storage and regulated secretion in hematopoietic cells.}}, url = {{http://dx.doi.org/10.1189/jlb.1103593}}, doi = {{10.1189/jlb.1103593}}, volume = {{76}}, year = {{2004}}, }