Targeting proteins to secretory lysosomes of natural killer cells as a principle for immunoregulation.
| العنوان: | Targeting proteins to secretory lysosomes of natural killer cells as a principle for immunoregulation. |
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| المؤلفون: | Hansson, Markus, Jönsson, Sofia, Persson, Ann-Maj, Calafat, Jero, Tapper, Hans, Olsson, Inge |
| المصدر: | Molecular Immunology. 40(6):363-372 |
| مصطلحات موضوعية: | Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Immunologi inom det medicinska området, Medical and Health Sciences, Basic Medicine, Immunology in the medical area |
| الوصف: | 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. |
| الوصول الحر: | https://lup.lub.lu.se/record/118352Test http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14522017&dopt=AbstractTest http://dx.doi.org/10.1016/S0161-5890Test(03)00151-2 |
| قاعدة البيانات: | SwePub |
| تدمد: | 18729142 |
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| DOI: | 10.1016/S0161-5890(03)00151-2 |