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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-10-3055. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3055v1 102/2/682    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gao, Y. Articles by Olsson, I. Search for Related Content PubMed PubMed Citation Articles by Gao, Y. Articles by Olsson, I. Related Collections Gene Therapy Hematopoiesis and Stem Cells Phagocytes Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2003, Vol. 102, No. 2, pp. 682-688 PHAGOCYTES Sorting of soluble TNF-receptor for granule storage in hematopoietic cells as a principle for targeting of selected proteins to inflamed sites Ying Gao, Hanna Rosén, Ellinor Johnsson, Jero Calafat, Hans Tapper, and Inge Olsson From the Department of Hematology and the Department of Cell and Molecular Biology, Lund, Sweden; and The Netherlands Cancer Institute, Amsterdam, the Netherlands Hematopoietic cells have secretory lysosomes that degranulate at the inflammatory site upon stimulation. We asked whether one could target exogenous proteins with a therapeutic potential to secretory lysosomes in hematopoietic cells. For this purpose, we expressed a soluble tumor necrosis factor (TNF) receptor form (sTNFR1) in hematopoietic cell lines. In order to accomplish targeting to secretory lysosomes, both endoplasmic reticulum (ER) retention and constitutive secretion have to be prevented. ER export was facilitated by addition of a transmembrane (tm) sequence, and constitutive secretion was overcome by incorporating a cytosolic sorting signal (Y) from CD63. This signal directed the resulting sTNFR1-tm-Y to secretory lysosomes. Confirmation of these results was provided by biosynthetic radiolabeling, subcellular fractionation, immunofluorescence microscopy, and immunoelectron microscopy. The tm-Y fragment was cleaved by proteolysis, resulting in generation of the membrane-free sTNFR1 in secretory lysosomes. Our results suggest a potential for using the storage organelles of hematopoietic cells as vehicles for targeting sites of inflammation with therapeutically active agents. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Hematopoietic cells for targeting iatrogenic immunomodulation William M. Nauseef Blood 2003 102: 418-419. [Full Text] [PDF] This article has been cited by other articles: M. N. A. Mandal, V. Vasireddy, G. B. Reddy, X. Wang, S. E. Moroi, B. R. Pattnaik, B. A. Hughes, J. R. Heckenlively, P. F. Hitchcock, M. M. Jablonski, et al. CTRP5 Is a Membrane-Associated and Secretory Protein in the RPE and Ciliary Body and the S163R Mutation of CTRP5 Impairs Its Secretion Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5505 - 5513. [Abstract] [Full Text] [PDF] Y. Gao, M. Hansson, J. Calafat, H. Tapper, and I. Olsson Sorting soluble tumor necrosis factor (TNF) receptor for storage and regulated secretion in hematopoietic cells J. Leukoc. Biol., October 1, 2004; 76(4): 876 - 885. [Abstract] [Full Text] [PDF]

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