This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pouvelle, B.
Right arrow Articles by Gysin, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pouvelle, B.
Right arrow Articles by Gysin, J.

 Previous Article  |  Next Article 

Infection and Immunity, July 2007, p. 3516-3522, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.01852-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Neural Cell Adhesion Molecule, a New Cytoadhesion Receptor for Plasmodium falciparum-Infected Erythrocytes Capable of Aggregation{triangledown}

Bruno Pouvelle,1* Valéry Matarazzo,2 Christophe Jurzynski,1 Johannes Nemeth,3,4,5 Michael Ramharter,3,4,5 Geneviève Rougon,2 and Jürg Gysin1

Unité de Parasitologie Expérimentale, EA3282 Institut Pasteur/Univ. Med., IFR48, Faculté de Médecine de la Timone, 27 Boulevard Jean Moulin, 13385 Marseille, France,1 Institut de Biologie du Développement de Marseille-Luminy, UMR CNRS 6216, Université de la Méditerranée case 907, Campus de Luminy, 13288 Marseille, France,2 Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon,3 Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany,4 Department of Internal Medicine I, Division of Infectious Diseases, Medical University of Vienna, Vienna, Austria5

Received 22 November 2006/ Returned for modification 2 January 2007/ Accepted 26 April 2007

The cytoadhesion of Plasmodium falciparum-infected erythrocytes (IEs) to the endothelial cells lining the microvasculature, clogging the microvessels of various organs, is a key event in the pathogenesis of certain severe forms of malaria, such as cerebral malaria and pulmonary edema. Studies aiming to identify possible correlations between the severity of clinical cases and the presence of particular cytoadhesion phenotypes have been largely unsuccessful. One of the possible reasons for this failure is that some of the key receptors and/or mechanisms involved have yet to be identified. By combining IE selection, cell transfection, and adhesion inhibition assays, we identified a new cytoadhesion receptor, neural cell adhesion molecule (NCAM). NCAM is a member of the immunoglobulin superfamily and has nonpolysialylated and polysialylated isoforms, the latter being rare in adults. The nonpolysialylated form is present on the surfaces of endothelial cells in the microvessels of various organs in which IE sequestration occurs. We found that multiphenotypic IEs interacted with nonpolysialylated NCAM and with another, as yet unidentified receptor. These IEs also displayed cytoadhesion in flow conditions, presenting the unique ability to form adherent macroaggregates composed of hundreds of IEs. These features may act as virulence factors, increasing the capacity of IEs to clog microvessels via receptor synergy and macroaggregate formation, thereby facilitating the pathogenesis of severe forms of malaria.

* Corresponding author. Mailing address: Unité de Parasitologie Expérimentale, EA 3282, Faculté de Médecine de la Timone, 27 Boulevard Jean Moulin, 13385 Marseille, France. Phone: 33-(0)4-91-32-46-04. Fax: 33-(0)4-91-32-46-34. E-mail: pouvelle{at}medecine.univ-mrs.fr

{triangledown} Published ahead of print on 7 May 2007.

Editor: J. F. Urban, Jr.

Infection and Immunity, July 2007, p. 3516-3522, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.01852-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»