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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.


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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 {alpha}IIb{beta}3, 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 {alpha}IIb{beta}3 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 {beta}3-deficient and wild-type mice were indistinguishable. These findings suggest that thrombocytopenia of relapsing fever is the result of platelet clearance after {beta}3-independent bacterial attachment to circulating platelets.


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