Targeting proteins to secretory lysosomes of natural killer cells as a principle for immunoregulation.
(2003) In Molecular Immunology 40(6). p.363-372- Abstract
- Secretory lysosomes of natural killer (NK) cells combine storage, regulated secretion and lysosomal activity. We asked whether one could target exogenous proteins to the secretory lysosomes of NK-cells for final delivery into a tumor site upon degranulation. cDNAs for both soluble and transmembrane (tm) proteins were expressed in the human YT-Indy NK-cell line. Targeting of a soluble TNF receptor (sTNFR1) was achieved by expressing a cDNA construct with a transmembrane sequence to facilitate ER-export and by incorporating a cytosolic sorting signal (Y) from CD63 to overcome constitutive secretion. The resulting sTNFR1-tm-Y was targeted to secretory lysosomes as confirmed by results from biosynthetic radiolabeling in combination with... (More)
- Secretory lysosomes of natural killer (NK) cells combine storage, regulated secretion and lysosomal activity. We asked whether one could target exogenous proteins to the secretory lysosomes of NK-cells for final delivery into a tumor site upon degranulation. cDNAs for both soluble and transmembrane (tm) proteins were expressed in the human YT-Indy NK-cell line. Targeting of a soluble TNF receptor (sTNFR1) was achieved by expressing a cDNA construct with a transmembrane sequence to facilitate ER-export and by incorporating a cytosolic sorting signal (Y) from CD63 to overcome constitutive secretion. The resulting sTNFR1-tm-Y was targeted to secretory lysosomes as confirmed by results from biosynthetic radiolabeling in combination with subcellular fractionation, immunoelectron microscopy, and immunofluorescence microscopy. A soluble sTNFR1 form was generated in the secretory lysosome by endogenous proteolytic activity. Expression of exogenous normally secretory non-membrane proteins, such as alpha1-microglobulin (alpha1-m) and alpha1-antitrypsin (alpha1-at) resulted mostly in constitutive secretion although a small amount of alpha1-microglobulin was targeted to secretory lysosomes. Our results suggest a potential for delivery of pharmacologically active agents into tumor sites by use of the NK-cell secretory lysosome as a carrier. (C) 2003 Elsevier Ltd. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/118352
- author
- Hansson, Markus LU ; Jönsson, Sofia LU ; Persson, Ann-Maj LU ; Calafat, Jero ; Tapper, Hans LU and Olsson, Inge LU
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Immunology
- volume
- 40
- issue
- 6
- pages
- 363 - 372
- publisher
- Pergamon Press Ltd.
- external identifiers
-
- wos:000185843000006
- scopus:0141533219
- ISSN
- 1872-9142
- DOI
- 10.1016/S0161-5890(03)00151-2
- language
- English
- LU publication?
- yes
- id
- 9e6ef65e-280f-480c-95c2-8ec585bac8f7 (old id 118352)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14522017&dopt=Abstract
- date added to LUP
- 2016-04-01 16:54:23
- date last changed
- 2024-04-26 11:44:58
@article{9e6ef65e-280f-480c-95c2-8ec585bac8f7, abstract = {{Secretory lysosomes of natural killer (NK) cells combine storage, regulated secretion and lysosomal activity. We asked whether one could target exogenous proteins to the secretory lysosomes of NK-cells for final delivery into a tumor site upon degranulation. cDNAs for both soluble and transmembrane (tm) proteins were expressed in the human YT-Indy NK-cell line. Targeting of a soluble TNF receptor (sTNFR1) was achieved by expressing a cDNA construct with a transmembrane sequence to facilitate ER-export and by incorporating a cytosolic sorting signal (Y) from CD63 to overcome constitutive secretion. The resulting sTNFR1-tm-Y was targeted to secretory lysosomes as confirmed by results from biosynthetic radiolabeling in combination with subcellular fractionation, immunoelectron microscopy, and immunofluorescence microscopy. A soluble sTNFR1 form was generated in the secretory lysosome by endogenous proteolytic activity. Expression of exogenous normally secretory non-membrane proteins, such as alpha1-microglobulin (alpha1-m) and alpha1-antitrypsin (alpha1-at) resulted mostly in constitutive secretion although a small amount of alpha1-microglobulin was targeted to secretory lysosomes. Our results suggest a potential for delivery of pharmacologically active agents into tumor sites by use of the NK-cell secretory lysosome as a carrier. (C) 2003 Elsevier Ltd. All rights reserved.}}, author = {{Hansson, Markus and Jönsson, Sofia and Persson, Ann-Maj and Calafat, Jero and Tapper, Hans and Olsson, Inge}}, issn = {{1872-9142}}, language = {{eng}}, number = {{6}}, pages = {{363--372}}, publisher = {{Pergamon Press Ltd.}}, series = {{Molecular Immunology}}, title = {{Targeting proteins to secretory lysosomes of natural killer cells as a principle for immunoregulation.}}, url = {{http://dx.doi.org/10.1016/S0161-5890(03)00151-2}}, doi = {{10.1016/S0161-5890(03)00151-2}}, volume = {{40}}, year = {{2003}}, }