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Prepublished online as a Blood First Edition Paper on November 27, 2002; DOI 10.1182/blood-2002-09-2841. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-09-2841v1 101/7/2850    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 Yipp, B. G. Articles by Ho, M. Search for Related Content PubMed PubMed Citation Articles by Yipp, B. G. Articles by Ho, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Red Cells Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 April 2003, Vol. 101, No. 7, pp. 2850-2857 RED CELLS Src-family kinase signaling modulates the adhesion of Plasmodium falciparum on human microvascular endothelium under flow Bryan G. Yipp, Stephen M. Robbins, Mary E. Resek, Dror I. Baruch, Sornchai Looareesuwan, and May Ho From the Immunology Research Group, Department of Microbiology and Infectious Diseases, and Departments of Oncology and Molecular Biology and Biochemistry, University of Calgary, AB, Canada; the Laboratory for Parasitic Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. The pathogenicity of Plasmodium falciparum is due to the unique ability of infected erythrocytes (IRBCs) to adhere to vascular endothelium. We investigated whether adhesion of IRBCs to CD36, the major cytoadherence receptor on human dermal microvascular endothelial cells (HDMECs), induces intracellular signaling and regulates adhesion. A recombinant peptide corresponding to the minimal CD36-binding domain from P falciparum erythrocyte membrane protein 1 (PfEMP1), as well as an anti-CD36 monoclonal antibody (mAb) that inhibits IRBC binding, activated the mitogen-activated protein (MAP) kinase pathway that was dependent on Src-family kinase activity. Treatment of HDMECs with a Src-family kinase-selective inhibitor (PP1) inhibited adhesion of IRBCs in a flow-chamber assay by 72% (P < .001). More importantly, Src-family kinase activity was also required for cytoadherence to intact human microvessels in a human/severe combined immunodeficient (SCID) mouse model in vivo. The effect of PP1 could be mimicked by levamisole, a specific alkaline-phosphatase inhibitor. Firm adhesion to PP1-treated endothelium was restored by exogenous alkaline phosphatase. In contrast, inhibition of the extracellular signal-regulated kinase 1/2 (ERK 1/2) and p38 MAP kinase pathways had no immediate effect on IRBC adhesion. These results suggest a novel mechanism for the modulation of cytoadherence under flow conditions through a signaling pathway involving CD36, Src-family kinases, and an ectoalkaline phosphatase. Targeting endothelial ectoalkaline phosphatases and/or signaling molecules may constitute a novel therapeutic strategy against severe falciparum malaria. © 2003 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: N. Day and A. M. Dondorp The Management of Patients with Severe Malaria Am J Trop Med Hyg, December 1, 2007; 77(6_Suppl): 29 - 35. [Abstract] [Full Text] [PDF] L. M. Stuart, S. A. Bell, C. R. Stewart, J. M. Silver, J. Richard, J. L. Goss, A. A. Tseng, A. Zhang, J. B. E. Khoury, and K. J. Moore CD36 Signals to the Actin Cytoskeleton and Regulates Microglial Migration via a p130Cas Complex J. Biol. Chem., September 14, 2007; 282(37): 27392 - 27401. [Abstract] [Full Text] [PDF] K. J. Moore and M. W. Freeman Scavenger Receptors in Atherosclerosis: Beyond Lipid Uptake Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1702 - 1711. [Abstract] [Full Text] [PDF] S. Munter, M. Way, and F. Frischknecht Signaling During Pathogen Infection Sci. Signal., May 16, 2006; 2006(335): re5 - re5. [Abstract] [Full Text] [PDF] S. C. Wassmer, V. Combes, F. J. Candal, I. Juhan-Vague, and G. E. Grau Platelets Potentiate Brain Endothelial Alterations Induced by Plasmodium falciparum Infect. Immun., January 1, 2006; 74(1): 645 - 653. [Abstract] [Full Text] [PDF] M. Ho, H. L. Hoang, K. M. Lee, N. Liu, T. MacRae, L. Montes, C. L. Flatt, B. G. Yipp, B. J. Berger, S. Looareesuwan, et al. Ectophosphorylation of CD36 Regulates Cytoadherence of Plasmodium falciparum to Microvascular Endothelium under Flow Conditions Infect. Immun., December 1, 2005; 73(12): 8179 - 8187. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020