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Prepublished online as a Blood First Edition Paper on August 15, 2002; DOI 10.1182/blood-2002-06-1725. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-06-1725v1 101/1/331    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 Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2003, Vol. 101, No. 1, pp. 331-337 RED CELLS Recombinant PfEMP1 peptide inhibits and reverses cytoadherence of clinical Plasmodium falciparum isolates in vivo Bryan G. Yipp, Dror I. Baruch, Ciaran Brady, Allan G. Murray, Sornchai Looareesuwan, Paul Kubes, and May Ho From the Immunology Research Group, University of Calgary, Calgary, AB, Canada; Laboratory for Parasitic Diseases and Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; Department of Medicine, University of Alberta, Edmonton, AB, Canada; and Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. The parasite ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and host endothelial receptors represent potential targets for antiadhesive therapy for cytoadherence. In the present study, the major host receptor CD36 was targeted in vitro and in vivo with a recombinant peptide, PpMC-179, corresponding to the minimal CD36-binding domain from the cysteine-rich interdomain region 1 (CIDR1) within the MCvar1 PfEMP1. The in vitro inhibitory effect of PpMC-179 on human dermal microvascular endothelial cells (HDMECs) expressing multiple relevant adhesion molecules was investigated using a parallel-plate flow chamber. Pretreatment of endothelial monolayers with PpMC-179 (2 µM) inhibited the adhesion of infected erythrocytes (IRBCs) from all clinical isolates tested by 84.4% on resting and 62.8% on tumor necrosis factor  (TNF-)-stimulated monolayers. Adhesion to stimulated cells was further inhibited (90.4%) when PpMC-179 was administered with an inhibitory anti-intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody 84H10 (5 µg/mL). To determine the in vivo effectiveness of PpMC-179, we used a human/severe combined immunodeficiency (SCID) mouse chimeric model that allowed direct visualization of cytoadherence on intact human microvasculature. In unstimulated skin grafts, PpMC-179 inhibited adhesion by 86.3% and by 84.6% in TNF--stimulated skin grafts. More importantly, PpMC-179 administration resulted in the detachment of already adherent IRBCs by 80.7% and 83.3% on resting and stimulated skin grafts, respectively. The antiadhesive effect of PpMC-179 was rapid and sustained in vivo for at least 30 minutes. Our data indicate that targeting cytoadhesion in vivo is feasible and may offer a rapid antimalarial therapy. © 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: M. Mo, H. C. Lee, M. Kotaka, M. Niang, X. Gao, J. K. Iyer, J. Lescar, and P. Preiser The C-Terminal Segment of the Cysteine-Rich Interdomain of Plasmodium falciparum Erythrocyte Membrane Protein 1 Determines CD36 Binding and Elicits Antibodies That Inhibit Adhesion of Parasite-Infected Erythrocytes Infect. Immun., May 1, 2008; 76(5): 1837 - 1847. [Abstract] [Full Text] [PDF] S. N. Patel, Z. Lu, K. Ayi, L. Serghides, D. C. Gowda, and K. C. Kain Disruption of CD36 Impairs Cytokine Response to Plasmodium falciparum Glycosylphosphatidylinositol and Confers Susceptibility to Severe and Fatal Malaria In Vivo J. Immunol., March 15, 2007; 178(6): 3954 - 3961. [Abstract] [Full Text] [PDF] M. U. Ferreira, M. da Silva Nunes, and G. Wunderlich Antigenic Diversity and Immune Evasion by Malaria Parasites Clin. Vaccine Immunol., November 1, 2004; 11(6): 987 - 995. [Full Text] [PDF] S. Gratepanche, B. Gamain, J. D. Smith, B. A. Robinson, A. Saul, and L. H. Miller Induction of crossreactive antibodies against the Plasmodium falciparum variant protein PNAS, October 28, 2003; 100(22): 13007 - 13012. [Abstract] [Full Text] [PDF] B. G. Yipp, S. M. Robbins, M. E. Resek, D. I. Baruch, S. Looareesuwan, and M. Ho Src-family kinase signaling modulates the adhesion of Plasmodium falciparum on human microvascular endothelium under flow Blood, April 1, 2003; 101(7): 2850 - 2857. [Abstract] [Full Text] [PDF]

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