The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 4167K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, Q.
Right arrow Articles by Wahlgren, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, Q.
Right arrow Articles by Wahlgren, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1998/1/15/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 1, January 5, 1998 15-23

Article

Identification of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) as the Rosetting Ligand of the Malaria Parasite P. falciparum

Qijun Chen*, Antonio Barragan*, Victor Fernandez*, Annika Sundström*, Martha Schlichtherle*, Anders Sahlén*, Johan Carlson*, Santanu Datta{ddagger}, and Mats Wahlgren*

From the * Microbiology and Tumor Biology Center, Karolinska Institutet, the Swedish Institute for Infectious Disease Control, S-171 77 Stockholm, Sweden; and {ddagger} Astra Research Centre, Bangalore, 560003, India

Severe Plasmodium falciparum malaria is characterized by excessive sequestration of infected and uninfected erythrocytes in the microvasculature of the affected organ. Rosetting, the adhesion of P. falciparum–infected erythrocytes to uninfected erythrocytes is a virulent parasite phenotype associated with the occurrence of severe malaria. Here we report on the identification by single-cell reverse transcriptase PCR and cDNA cloning of the adhesive ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting PfEMP1 contains clusters of glycosaminoglycan-binding motifs. A recombinant fusion protein (Duffy binding-like 1–glutathione S transferase; Duffy binding-like-1–GST) was found to adhere directly to normal erythrocytes, disrupt naturally formed rosettes, block rosette reformation, and bind to a heparin-Sepharose matrix. The adhesive interactions could be inhibited with heparan sulfate or enzymes that remove heparan sulfate from the cell surface whereas other enzymes or similar glycosaminoglycans of a like negative charge did not affect the binding. PfEMP1 is suggested to be the rosetting ligand and heparan sulfate, or a heparan sulfate–like molecule, the receptor both for PfEMP1 binding and naturally formed erythrocyte rosettes.

Address correspondence to Mats Wahlgren, the Microbiology and Tumor Biology Center, Karolinska Institutet, the Swedish Institute for Infectious Disease Control, Box 280, S-171 77 Stockholm, Sweden. Phone: 46-8-728-72-77; FAX: 46-8-33-15-47; E-mail: mats.wahlgren{at}smi.ki.se.

1 Abbreviations used in this paper: aa, amino acid; ATS, acidic COOH-terminal segment; CIDR, cysteine-rich interdomain region; DBL, Duffy binding-like; GAG, glycosaminoglycan; GST, glutathione S transferase; mRNA, messenger RNA; PfEMP 1, Plasmodium falciparum erythrocyte membrane protein 1; pRBC, parasitized RBC; RT-PCR, reverse transcriptase PCR; TM, transmembrane.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS