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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4478-4486. Prepublished online as a Blood First Edition Paper on February 1, 2007; DOI 10.1182/blood-2006-02-001719. This Article Full Text (PDF) All Versions of this Article: blood-2006-02-001719v1 109/10/4478    most recent Alert me when this article is cited Alert me if a correction is posted 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 Niemann, C. U. Articles by Borregaard, N. Search for Related Content PubMed PubMed Citation Articles by Niemann, C. U. Articles by Borregaard, N. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 6, 2006 Accepted January 23, 2007 Neutrophil elastase depends on serglycin proteoglycan for localization in granules Carsten U. Niemann*, Magnus Abrink, Gunnar Pejler, Rikke L. Fischer, Erik I. Christensen, Stefan D. Knight, and Niels Borregaard Rigshospitalet, Department of Hematology, The Granulocyte Research Laboratory, University of Copenhagen, Copenhagen, Denmark Department of Molecular Biosciences, Uppsala Biomedical Centre, Swedish University of Agricultural Sciences, Uppsala, Sweden National Center for Antimicrobials and Infectious Control, Statens Serum Institut, Copenhagen, Denmark Department of Cell Biology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark Department of Molecular Biology, Uppsala Biomedical Centre, Swedish University of Agricultural Sciences, Uppsala, Sweden * Corresponding author; email: niemann{at}dadlnet.dk. Granule proteins play a major role in bacterial killing by neutrophils. Serglycin proteoglycan, the major intracellular proteoglycan of hematopoietic cells, has been proposed to play a role in sorting and packing of granule proteins. We examined the content of major neutrophil granule proteins in serglycin knock-out mice and found neutrophil elastase absent from mature neutrophils as shown by activity assay, Western blotting, and immunocytochemistry, whereas neutrophil elastase mRNA was present. The localization of other neutrophil granule proteins did not differ between wild type and serglycin knock-out mice. Differential counts and neutrophil ultrastructure were unaffected by the lack of serglycin, indicating that defective localization of neutrophil elastase does not induce neutropenia itself, albeit mutations in the neutrophil elastase gene can cause severe congenital neutropenia or cyclic neutropenia. The virulence of intraperitoneally injected Gram-negative bacteria (Klebsiella pneumoniae) was increased in serglycin knock-out mice compared with wild type mice, as previously reported for neutrophil elastase knock-out mice. Thus, serglycin proteoglycan has an important role in localizing neutrophil elastase in azurophil granules of neutrophils, while localization of other granule proteins must be mediated by other mechanisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Duelli, E. Ronnberg, I. Waern, M. Ringvall, S. O. Kolset, and G. Pejler Mast Cell Differentiation and Activation Is Closely Linked to Expression of Genes Coding for the Serglycin Proteoglycan Core Protein and a Distinct Set of Chondroitin Sulfate and Heparin Sulfotransferases J. Immunol., December 1, 2009; 183(11): 7073 - 7083. [Abstract] [Full Text] [PDF] C. A. Kunder, A. L. St. John, G. Li, K. W. Leong, B. Berwin, H. F. Staats, and S. N. Abraham Mast cell-derived particles deliver peripheral signals to remote lymph nodes J. Exp. Med., October 26, 2009; 206(11): 2455 - 2467. [Abstract] [Full Text] [PDF] S. Wernersson, T. Braga, O. Sawesi, I. Waern, K. E. Nilsson, G. Pejler, and M. Abrink Age-related enlargement of lymphoid tissue and altered leukocyte composition in serglycin-deficient mice J. Leukoc. Biol., March 1, 2009; 85(3): 401 - 408. [Abstract] [Full Text] [PDF] L. Kallquist, M. Hansson, A.-M. Persson, H. Janssen, J. Calafat, H. Tapper, and I. Olsson The tetraspanin CD63 is involved in granule targeting of neutrophil elastase Blood, October 15, 2008; 112(8): 3444 - 3454. [Abstract] [Full Text] [PDF] M. Grujic, J. P. Christensen, M. R. Sorensen, M. Abrink, G. Pejler, and A. R. Thomsen Delayed Contraction of the CD8+ T Cell Response toward Lymphocytic Choriomeningitis Virus Infection in Mice Lacking Serglycin J. Immunol., July 15, 2008; 181(2): 1043 - 1051. [Abstract] [Full Text] [PDF] D. S. Woulfe, J. K. Lilliendahl, S. August, L. Rauova, M. A. Kowalska, M. Abrink, G. Pejler, J. G. White, and B. P. Schick Serglycin proteoglycan deletion induces defects in platelet aggregation and thrombus formation in mice Blood, April 1, 2008; 111(7): 3458 - 3467. [Abstract] [Full Text] [PDF]

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