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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 (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 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. Social Bookmarking                   What's this? Submitted June 12, 2002 Accepted July 31, 2002 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* Microbiology and Infectious Diseases/immunology Research Group, University of Calgary, Calgary, AB, Canada Laboratory for Parasitic Diseaes, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA Department of Medicine, University of Alberta, Edmonton, AB, Canada Faculty of Tropical Medicine, Mahidol University, Bangkok, -, Thailand * Corresponding author; email: mho{at}ucalgary.ca. The parasite ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and host endothelial receptors represent potential targets for anti-adhesive 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 endothelium (HDMEC) expressing multiple relevant adhesion molecules was investigated using a parallel plate flow chamber. Pre-treatment of endothelial monolayers with PpMC-179 (2 micromolar) inhibited the adhesion of infected erythrocytes (IRBC) from all clinical isolates tested by 84.4% on resting and 62.8% on TNF--stimulated monolayers. Adhesion to stimulated cells was further inhibited (90.4%) when PpMC-179 was administered with an inhibitory anti-ICAM-1 mAb 84H10 (5 µg/ml). To determine the in vivo effectiveness of PpMC-179, we used a human/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 84.6 % in TNF--stimulated skin grafts. More importantly, PpMC-179 administration resulted in the detachment of already adherent IRBC by 80.7% and 83.3 % on resting and stimulated skin grafts respectively. The anti-adhesive effect of PpMC-179 was rapid and sustained in vivo for at least 30 minutes. Our data indicate that targeting cytoadherence in vivo is feasible and may offer a rapid antimalarial therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Faille, V. Combes, A. J. Mitchell, A. Fontaine, I. Juhan-Vague, M.-C. Alessi, G. Chimini, T. Fusai, and G. E. 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020