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Blood, 1 March 2005, Vol. 105, No. 5, pp. 1956-1963. Prepublished online as a Blood First Edition Paper on October 19, 2004; DOI 10.1182/blood-2004-06-2206. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2206v1 105/5/1956    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 van der Heyde, H. C. Articles by Woods, C. Search for Related Content PubMed PubMed Citation Articles by van der Heyde, H. C. Articles by Woods, C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Red Cells Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Platelet depletion by anti-CD41 (IIb) mAb injection early but not late in the course of disease protects against Plasmodium berghei pathogenesis by altering the levels of pathogenic cytokines Henri C. van der Heyde, Irene Gramaglia, Guang Sun, and Catherine Woods From the La Jolla Bioengineering Institute and Targeted Molecules Corporation, San Diego, CA; and the Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA. Accumulating evidence indicates that platelets play a critical role in the pathogenesis of experimental severe malaria (ESM) elicited by infection with Plasmodium berghei. Mice injected on day 1 of P berghei infection (early) with either anti-CD41 or anti-CD61 monoclonal antibodies (mAbs) exhibited significantly (P < .001) increased survival from ESM compared with infection controls, indicating that platelets function early in the disease. In contrast, groups of mice treated on days 4, 5, and 6 (late) with anti-CD41 mAb exhibited similar mortality as controls. Because platelet depletion by anti-CD41 mAb on day 4 of infection did not protect mice, and platelet adherence occurs on day 6, platelet adherence to endothelium is not required to mediate malarial pathogenesis. Few platelet microparticles were detected in the blood during the course of malaria, but large numbers of erythrocyte vesicles, microparticles, and debris were detected. The protective effect of early anti-CD41 mAb treatment was independent of the number of platelets, platelet microparticles, erythrocyte-platelet conjugates, and erythrocyte vesicles. Mice treated early with anti-CD41 mAb exhibited markedly altered cytokine production on day 4 of P berghei infection (increased interleukin 10 [IL-10], IL-1, IL-6, interferon- [IFN-], and tumor necrosis factor [TNF-]; decreased IL-2) but no decline in coagulation factors compared with rat immunoglobulin G (IgG)–treated controls, indicating that platelets regulate the levels of pathogenic cytokines. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. M. Randall, F. H. Amante, K. A. McSweeney, Y. Zhou, A. C. Stanley, A. Haque, M. K. Jones, G. R. Hill, G. M. Boyle, and C. R. Engwerda Common Strategies To Prevent and Modulate Experimental Cerebral Malaria in Mouse Strains with Different Susceptibilities Infect. Immun., July 1, 2008; 76(7): 3312 - 3320. [Abstract] [Full Text] [PDF] M.-F. Penet, M. Abou-Hamdan, N. Coltel, E. Cornille, G. E. Grau, M. de Reggi, and B. Gharib Protection against cerebral malaria by the low-molecular-weight thiol pantethine PNAS, January 29, 2008; 105(4): 1321 - 1326. [Abstract] [Full Text] [PDF] D. Simberg, T. Duza, J. H. Park, M. Essler, J. Pilch, L. Zhang, A. M. Derfus, M. Yang, R. M. Hoffman, S. Bhatia, et al. Biomimetic amplification of nanoparticle homing to tumors PNAS, January 16, 2007; 104(3): 932 - 936. [Abstract] [Full Text] [PDF] C. CASALS-PASCUAL, O. KAI, C. R. J. C. NEWTON, N. PESHU, and D. J. ROBERTS THROMBOCYTOPENIA IN FALCIPARUM MALARIA IS ASSOCIATED WITH HIGH CONCENTRATIONS OF IL-10. Am J Trop Med Hyg, September 1, 2006; 75(3): 434 - 436. [Abstract] [Full Text] [PDF] I. Gramaglia, H. Sahlin, J. P. Nolan, J. A. Frangos, M. Intaglietta, and H. C. van der Heyde Cell- Rather Than Antibody-Mediated Immunity Leads to the Development of Profound Thrombocytopenia during Experimental Plasmodium berghei Malaria J. Immunol., December 1, 2005; 175(11): 7699 - 7707. [Abstract] [Full Text] [PDF]

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