SEARCH:   Advanced

This Article Full Text Full Text (PDF) 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 Nieswandt, B. Articles by Zirngibl, H. Search for Related Content PubMed PubMed Citation Articles by Nieswandt, B. Articles by Zirngibl, H. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 October 2000, Vol. 96, No. 7, pp. 2520-2527 IMMUNOBIOLOGY Identification of critical antigen-specific mechanisms in the development of immune thrombocytopenic purpura in mice Bernhard Nieswandt, Wolfgang Bergmeier, Kirsten Rackebrandt, J. Engelbert Gessner, and Hubert Zirngibl From the Department of Molecular Oncology, General Surgery, University of Witten-Herdecke, Wuppertal, Germany; and Department of Clinical Immunology, Hannover Medical School, Hannover, Germany. The pathogenic effects of antiplatelet antibodies were investigated in mice. Monoclonal antibodies (mAbs) of different immunoglobulin G subclass directed against mouse GPIIbIIIa, GPIIIa, GPIb, GPIb-IX, GPV, and CD31 were generated and characterized biochemically. MAbs against GPIb-IX, GPV, CD31, and linear epitopes on GPIIIa had mild and transient effects on platelet counts and induced no spontaneous bleeding. Anti-GPIb mAbs induced profound irreversible thrombocytopenia (< 3% of normal) by Fc-independent mechanisms but only had minor effects on hematocrits. In contrast, injection of intact mAbs, but not F(ab)2 fragments, against conformational epitopes on GPIIbIIIa, induced irreversible thrombocytopenia, acute systemic reactions, hypothermia, decreased hematocrits, and a paradoxical loss of surface GPIIbIIIa on platelets in vivo, the latter suggesting the formation of platelet-derived microparticles. Blockage of platelet-activating factor receptors inhibited the acute reactions, but not thrombocytopenia, loss of GPIIbIIIa, and decreases in hematocrits. Repeated injections of low doses of anti-GPIIbIIIa antibodies resulted in profound thrombocytopenia and bleeding, whereas no acute systemic reactions were observed. These data strongly suggest that the identity of the target antigen recognized by antiplatelet antibodies determines the mechanisms of platelet destruction and the severity of bleeding in mice, the latter depending on previously unrecognized anti-GPIIbIIIa-specific inflammatory mechanisms. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Paruchuri, H. Tashimo, C. Feng, A. Maekawa, W. Xing, Y. Jiang, Y. Kanaoka, P. Conley, and J. A. Boyce Leukotriene E4-induced pulmonary inflammation is mediated by the P2Y12 receptor J. Exp. Med., October 26, 2009; 206(11): 2543 - 2555. [Abstract] [Full Text] [PDF] B. Ho-Tin-Noe, C. Carbo, M. Demers, S. M. Cifuni, T. Goerge, and D. D. Wagner Innate Immune Cells Induce Hemorrhage in Tumors during Thrombocytopenia Am. J. Pathol., October 1, 2009; 175(4): 1699 - 1708. [Abstract] [Full Text] [PDF] J. Hirahashi, K. Hishikawa, S. Kaname, N. Tsuboi, Y. Wang, D. I. Simon, G. Stavrakis, T. Shimosawa, L. Xiao, Y. Nagahama, et al. Mac-1 (CD11b/CD18) Links Inflammation and Thrombosis After Glomerular Injury Circulation, September 29, 2009; 120(13): 1255 - 1265. [Abstract] [Full Text] [PDF] C. Strassel, A. Eckly, C. Leon, C. Petitjean, M. Freund, J.-P. Cazenave, C. Gachet, and F. Lanza Intrinsic impaired proplatelet formation and microtubule coil assembly of megakaryocytes in a mouse model of Bernard-Soulier syndrome Haematologica, June 1, 2009; 94(6): 800 - 810. [Abstract] [Full Text] [PDF] J. Schroder, R. Lullmann-Rauch, N. Himmerkus, I. Pleines, B. Nieswandt, Z. Orinska, F. Koch-Nolte, B. Schroder, M. Bleich, and P. Saftig Deficiency of the Tetraspanin CD63 Associated with Kidney Pathology but Normal Lysosomal Function Mol. Cell. Biol., February 15, 2009; 29(4): 1083 - 1094. [Abstract] [Full Text] [PDF] A. Braun, J. E. Gessner, D. Varga-Szabo, S. N. Syed, S. Konrad, D. Stegner, T. Vogtle, R. E. Schmidt, and B. Nieswandt STIM1 is essential for Fc{gamma} receptor activation and autoimmune inflammation Blood, January 29, 2009; 113(5): 1097 - 1104. [Abstract] [Full Text] [PDF] A. K. Chauhan, J. Kisucka, A. Brill, M. T. Walsh, F. Scheiflinger, and D. D. Wagner ADAMTS13: a new link between thrombosis and inflammation J. Exp. Med., September 1, 2008; 205(9): 2065 - 2074. [Abstract] [Full Text] [PDF] B. Ho-Tin-Noe, T. Goerge, S. M. Cifuni, D. Duerschmied, and D. D. Wagner Platelet Granule Secretion Continuously Prevents Intratumor Hemorrhage Cancer Res., August 15, 2008; 68(16): 6851 - 6858. [Abstract] [Full Text] [PDF] B. Nieswandt How do platelets prevent bleeding? Blood, May 15, 2008; 111(10): 4835 - 4835. [Full Text] [PDF] T. Goerge, B. Ho-Tin-Noe, C. Carbo, C. Benarafa, E. Remold-O'Donnell, B.-Q. Zhao, S. M. Cifuni, and D. D. Wagner Inflammation induces hemorrhage in thrombocytopenia Blood, May 15, 2008; 111(10): 4958 - 4964. [Abstract] [Full Text] [PDF] C. Kleinschnitz, S. Braeuninger, M. Pham, M. Austinat, I. Nolte, T. Renne, B. Nieswandt, M. Bendszus, and G. Stoll Blocking of Platelets or Intrinsic Coagulation Pathway-Driven Thrombosis Does Not Prevent Cerebral Infarctions Induced by Photothrombosis Stroke, April 1, 2008; 39(4): 1262 - 1268. [Abstract] [Full Text] [PDF] B. D. Elzey, N. W. Schmidt, S. A. Crist, T. P. Kresowik, J. T. Harty, B. Nieswandt, and T. L. Ratliff Platelet-derived CD154 enables T-cell priming and protection against Listeria monocytogenes challenge Blood, April 1, 2008; 111(7): 3684 - 3691. [Abstract] [Full Text] [PDF] K. Venkataraman, Y.-M. Lee, J. Michaud, S. Thangada, Y. Ai, H. L. Bonkovsky, N. S. Parikh, C. Habrukowich, and T. Hla Vascular Endothelium As a Contributor of Plasma Sphingosine 1-Phosphate Circ. Res., March 28, 2008; 102(6): 669 - 676. [Abstract] [Full Text] [PDF] S. H. Slofstra, M. F. Bijlsma, A. P. Groot, P. H. Reitsma, T. Lindhout, H. ten Cate, and C. A. Spek Protease-activated receptor-4 inhibition protects from multiorgan failure in a murine model of systemic inflammation Blood, November 1, 2007; 110(9): 3176 - 3182. [Abstract] [Full Text] [PDF] T. S. Dhanjal, C. Pendaries, E. A. Ross, M. K. Larson, M. B. Protty, C. D. Buckley, and S. P. Watson A novel role for PECAM-1 in megakaryocytokinesis and recovery of platelet counts in thrombocytopenic mice Blood, May 15, 2007; 109(10): 4237 - 4244. [Abstract] [Full Text] [PDF] C. Kleinschnitz, M. Pozgajova, M. Pham, M. Bendszus, B. Nieswandt, and G. Stoll Targeting Platelets in Acute Experimental Stroke: Impact of Glycoprotein Ib, VI, and IIb/IIIa Blockade on Infarct Size, Functional Outcome, and Intracranial Bleeding Circulation, May 1, 2007; 115(17): 2323 - 2330. [Abstract] [Full Text] [PDF] R. S. Go, K. L. Johnston, and K. C. Bruden The association between platelet autoantibody specificity and response to intravenous immunoglobulin G in the treatment of patients with immune thrombocytopenia Haematologica, February 1, 2007; 92(2): 283 - 284. [Abstract] [Full Text] [PDF] Z. Li, R. E. Rumbaut, A. R. Burns, and C. W. Smith Platelet Response to Corneal Abrasion Is Necessary for Acute Inflammation and Efficient Re-epithelialization Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4794 - 4802. [Abstract] [Full Text] [PDF] M. L. Webster, E. Sayeh, M. Crow, P. Chen, B. Nieswandt, J. Freedman, and H. Ni Relative efficacy of intravenous immunoglobulin G in ameliorating thrombocytopenia induced by antiplatelet GPIIbIIIa versus GPIb{alpha} antibodies Blood, August 1, 2006; 108(3): 943 - 946. [Abstract] [Full Text] [PDF] V. Schulte, H. P. Reusch, M. Pozgajova, D. Varga-Szabo, C. Gachet, and B. Nieswandt Two-Phase Antithrombotic Protection After Anti-Glycoprotein VI Treatment in Mice Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1640 - 1647. [Abstract] [Full Text] [PDF] J. Kisucka, C. E. Butterfield, D. G. Duda, S. C. Eichenberger, S. Saffaripour, J. Ware, Z. M. Ruggeri, R. K. Jain, J. Folkman, and D. D. Wagner Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage PNAS, January 24, 2006; 103(4): 855 - 860. [Abstract] [Full Text] [PDF] T. Rabie, A. Strehl, A. Ludwig, and B. Nieswandt Evidence for a Role of ADAM17 (TACE) in the Regulation of Platelet Glycoprotein V J. Biol. Chem., April 15, 2005; 280(15): 14462 - 14468. [Abstract] [Full Text] [PDF] A. Musaji, F. Cormont, G. Thirion, C. L. Cambiaso, and J.-P. Coutelier Exacerbation of autoantibody-mediated thrombocytopenic purpura by infection with mouse viruses Blood, October 1, 2004; 104(7): 2102 - 2106. [Abstract] [Full Text] [PDF] S. Gruner, M. Prostredna, V. Schulte, T. Krieg, B. Eckes, C. Brakebusch, and B. Nieswandt Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo Blood, December 1, 2003; 102(12): 4021 - 4027. [Abstract] [Full Text] [PDF] W. Bergmeier, P. C. Burger, C. L. Piffath, K. M. Hoffmeister, J. H. Hartwig, B. Nieswandt, and D. D. Wagner Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro-aged or -injured mouse platelets Blood, December 1, 2003; 102(12): 4229 - 4235. [Abstract] [Full Text] [PDF] B. Nieswandt, W. Bergmeier, V. Schulte, T. Takai, U. Baumann, R. E. Schmidt, H. Zirngibl, W. Bloch, and J. E. Gessner Targeting of platelet integrin {alpha}IIb{beta}3 determines systemic reaction and bleeding in murine thrombocytopenia regulated by activating and inhibitory Fc{gamma}R Int. Immunol., March 1, 2003; 15(3): 341 - 349. [Abstract] [Full Text] [PDF] S. Massberg, M. Gawaz, S. Gruner, V. Schulte, I. Konrad, D. Zohlnhofer, U. Heinzmann, and B. Nieswandt A Crucial Role of Glycoprotein VI for Platelet Recruitment to the Injured Arterial Wall In Vivo J. Exp. Med., January 6, 2003; 197(1): 41 - 49. [Abstract] [Full Text] [PDF] Y. Kaluzhny, G. Yu, S. Sun, P. A. Toselli, B. Nieswandt, C. W. Jackson, and K. Ravid BclxL overexpression in megakaryocytes leads to impaired platelet fragmentation Blood, August 13, 2002; 100(5): 1670 - 1678. [Abstract] [Full Text] [PDF] O. Holtkotter, B. Nieswandt, N. Smyth, W. Muller, M. Hafner, V. Schulte, T. Krieg, and B. Eckes Integrin alpha 2-Deficient Mice Develop Normally, Are Fertile, but Display Partially Defective Platelet Interaction with Collagen J. Biol. Chem., March 22, 2002; 277(13): 10789 - 10794. [Abstract] [Full Text] [PDF] M.-P. Gratacap, B. Payrastre, B. Nieswandt, and S. Offermanns Differential Regulation of Rho and Rac through Heterotrimeric G-proteins and Cyclic Nucleotides J. Biol. Chem., December 14, 2001; 276(51): 47906 - 47913. [Abstract] [Full Text] [PDF] S. Kosugi, Y. Tomiyama, S. Honda, H. Kato, T. Kiyoi, H. Kashiwagi, Y. Kurata, and Y. Matsuzawa Platelet-associated anti-GPIIb-IIIa autoantibodies in chronic immune thrombocytopenic purpura recognizing epitopes close to the ligand-binding site of glycoprotein (GP) IIb Blood, September 15, 2001; 98(6): 1819 - 1827. [Abstract] [Full Text] [PDF] S. Moog, P. Mangin, N. Lenain, C. Strassel, C. Ravanat, S. Schuhler, M. Freund, M. Santer, M. Kahn, B. Nieswandt, et al. Platelet glycoprotein V binds to collagen and participates in platelet adhesion and aggregation Blood, August 15, 2001; 98(4): 1038 - 1046. [Abstract] [Full Text] [PDF] J. L. Teeling, T. Jansen-Hendriks, T. W. Kuijpers, M. de Haas, J. G. J. van de Winkel, C. E. Hack, and W. K. Bleeker Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia Blood, August 15, 2001; 98(4): 1095 - 1099. [Abstract] [Full Text] [PDF] R. J. Hansen and J. P. Balthasar Pharmacokinetics, Pharmacodynamics, and Platelet Binding of an Anti-Glycoprotein IIb/IIIa Monoclonal Antibody (7E3) in the Rat: A Quantitative Rat Model of Immune Thrombocytopenic Purpura J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 165 - 171. [Abstract] [Full Text] B. Nieswandt, W. Bergmeier, A. Eckly, V. Schulte, P. Ohlmann, J.-P. Cazenave, H. Zirngibl, S. Offermanns, and C. Gachet Evidence for cross-talk between glycoprotein VI and Gi-coupled receptors during collagen-induced platelet aggregation Blood, June 15, 2001; 97(12): 3829 - 3835. [Abstract] [Full Text] [PDF] B. Nieswandt, V. Schulte, W. Bergmeier, R. Mokhtari-Nejad, K. Rackebrandt, J.-P. Cazenave, P. Ohlmann, C. Gachet, and H. Zirngibl Long-Term Antithrombotic Protection by in Vivo Depletion of Platelet Glycoprotein VI in Mice J. Exp. Med., February 19, 2001; 193(4): 459 - 470. [Abstract] [Full Text] [PDF] W. Bergmeier, D. Bouvard, J. A. Eble, R. Mokhtari-Nejad, V. Schulte, H. Zirngibl, C. Brakebusch, R. Fassler, and B. Nieswandt Rhodocytin (Aggretin) Activates Platelets Lacking alpha 2beta 1 Integrin, Glycoprotein VI, and the Ligand-binding Domain of Glycoprotein Ibalpha J. Biol. Chem., June 29, 2001; 276(27): 25121 - 25126. [Abstract] [Full Text] [PDF]

	Copyright © 2000 by American Society of Hematology         Online ISSN: 1528-0020