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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3458-3467. Prepublished online as a Blood First Edition Paper on December 19, 2007; DOI 10.1182/blood-2007-07-104703. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-07-104703v1 111/7/3458    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 Google Scholar Articles by Woulfe, D. S. Articles by Schick, B. P. PubMed PubMed Citation Articles by Woulfe, D. S. Articles by Schick, B. P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Serglycin proteoglycan deletion induces defects in platelet aggregation and thrombus formation in mice Donna S. Woulfe1, Joanne Klimas Lilliendahl2, Shelley August1, Lubica Rauova3, M. Anna Kowalska3, Magnus Åbrink4, Gunnar Pejler5, James G. White6, and Barbara P. Schick2 1 Center for Translational Research and 2 Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA; 3 Department of Pediatrics, Children's Hospital of Pennsylvania, Philadelphia; 4 Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; 5 Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden; and 6 Pathology Department, University of Minnesota School of Medicine, Minneapolis Serglycin (SG), the hematopoietic cell secretory granule proteoglycan, is crucial for storage of specific secretory proteins in mast cells, neutrophils, and cytotoxic T lymphocytes. We addressed the role of SG in platelets using SG–/– mice. Wild-type (WT) but not SG–/– platelets contained chondroitin sulfate proteoglycans. Electron microscopy revealed normal -granule structure in SG–/– platelets. However, SG–/– platelets and megakaryocytes contained unusual scroll-like membranous inclusions, and SG–/– megakaryocytes showed extensive emperipolesis of neutrophils. SG–/– platelets had reduced ability to aggregate in response to low concentrations of collagen or PAR4 thrombin receptor agonist AYPGKF, and reduced fibrinogen binding after AYPGKF, but aggregated normally to ADP. 3H-serotonin and ATP secretion were greatly reduced in SG–/– platelets. The -granule proteins platelet factor 4, β-thromboglobulin, and platelet-derived growth factor were profoundly reduced in SG–/– platelets. Exposure of P-selectin and IIb after thrombin treatment was similar in WT and SG–/– platelets. SG–/– mice exhibited reduced carotid artery thrombus formation after exposure to FeCl3. This study demonstrates that SG is crucial for platelet function and thrombus formation. We propose that SG–/– platelet function deficiencies are related to inadequate packaging and secretion of selected -granule proteins and reduced secretion of dense granule contents critical for platelet activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Platelet proteoglycans packing it in Robert Flaumenhaft Blood 2008 111: 3308-3309. [Full Text] [PDF] This article has been cited by other articles: 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]

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