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Blood, 15 October 2003, Vol. 102, No. 8, pp. 2843-2850. Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-02-0426. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-02-0426v1 102/8/2843    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 Alugupalli, K. R. Articles by Leong, J. M. Search for Related Content PubMed PubMed Citation Articles by Alugupalli, K. R. Articles by Leong, J. M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Spirochete-platelet attachment and thrombocytopenia in murine relapsing fever borreliosis Kishore R. Alugupalli, Alan D. Michelson, Isabelle Joris, Tom G. Schwan, Kairbaan Hodivala-Dilke, Richard O. Hynes, and John M. Leong From the Department of Molecular Genetics and Microbiology, Center for Platelet Function Studies/Department of Pediatrics, and Department of Pathology, University of Massachusetts Medical School, Worcester, MA; Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT; and Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA. Thrombocytopenia is common in persons infected with relapsing fever Borreliae. We previously showed that the relapsing fever spirochete Borrelia hermsii binds to and activates human platelets in vitro and that, after platelet activation, high-level spirochete-platelet attachment is mediated by integrin IIb3, a receptor that requires platelet activation for full function. Here we established that B hermsii infection of the mouse results in severe thrombocytopenia and a functional defect in hemostasis caused by accelerated platelet loss. Disseminated intravascular coagulation, immune thrombocytopenic purpura, or splenic sequestration did not play a discernible role in this model. Instead, spirochete-platelet complexes were detected in the blood of infected mice, suggesting that platelet attachment by bacteria might result in platelet clearance. Consistent with this, splenomegaly and thrombocytopenia temporally correlated with spirochetemia, and the severity of thrombocytopenia directly correlated with the degree of spirochetemia. Activation of platelets and integrin IIb3 were apparently not required for bacterium-platelet binding or platelet clearance because the bacterium-bound platelets in the circulation were not activated, and platelet binding and thrombocytopenia during infection of 3-deficient and wild-type mice were indistinguishable. These findings suggest that thrombocytopenia of relapsing fever is the result of platelet clearance after 3-independent bacterial attachment to circulating platelets. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. C. MacNamara, R. Racine, M. Chatterjee, D. Borjesson, and G. M. 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Akira, E. Lien, and J. M. Leong MyD88- and Bruton's Tyrosine Kinase-Mediated Signals Are Essential for T Cell-Independent Pathogen-Specific IgM Responses J. Immunol., March 15, 2007; 178(6): 3740 - 3749. [Abstract] [Full Text] [PDF] D. D. Bolz, R. S. Sundsbak, Y. Ma, S. Akira, J. H. Weis, T. G. Schwan, and J. J. Weis Dual Role of MyD88 in Rapid Clearance of Relapsing Fever Borrelia spp. Infect. Immun., December 1, 2006; 74(12): 6750 - 6760. [Abstract] [Full Text] [PDF] K. M. Hovis, M. E. Schriefer, S. Bahlani, and R. T. Marconi Immunological and Molecular Analyses of the Borrelia hermsii Factor H and Factor H-Like Protein 1 Binding Protein, FhbA: Demonstration of Its Utility as a Diagnostic Marker and Epidemiological Tool for Tick-Borne Relapsing Fever. Infect. Immun., August 1, 2006; 74(8): 4519 - 4529. [Abstract] [Full Text] [PDF]

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