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Infection and Immunity, July 2005, p. 4288-4294, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4288-4294.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Inhibition of Chondroitin-4-Sulfate-Specific Adhesion of Plasmodium falciparum-Infected Erythrocytes by Sulfated Polysaccharides

Katherine T. Andrews,1* Nicole Klatt,2 Yvonne Adams,2 Petra Mischnick,3 and Reinhard Schwartz-Albiez4

Clinical Tropical Medicine Laboratory and The Australian Centre for International and Tropical Health and Nutrition (ACITHN), Queensland Institute of Medical Research, P.O. Box Royal Brisbane Hospital, Herston, 4029, Australia,1 Hygiene-Institut, Abteilung Parasitologie, Universität Heidelberg, Im Neuenheimer Feld 324,2 Deutsches Krebsforschungszentrum, Tumorimmunologie, Im Neuenheimer Feld 280, 69120 Heidelberg,4 Institut für Lebensmittelchemie, Technische Universität Braunschweig, Schleinitzstrasse 20, D-38106 Braunschweig, Germany3

Received 28 December 2004/ Returned for modification 23 January 2005/ Accepted 3 February 2005

Adhesion of Plasmodium falciparum-infected erythrocytes to placental chondroitin 4-sulfate (CSA) has been linked to the severe disease outcome of pregnancy-associated malaria. Soluble polysaccharides that release mature-stage parasitized erythrocytes into the peripheral circulation may help elucidate these interactions and have the potential to aid in developing therapeutic strategies. We have screened a panel of 11 sulfated polysaccharides for their capacities to inhibit adhesion of infected erythrocytes to CSA expressed on CHO-K1 cells and ex vivo human placental tissue. Two carrageenans and a cellulose sulfate (CS10) were able to inhibit adhesion to CSA and to cause already bound infected erythrocytes to de-adhere in a dose-dependent manner. CS10, like CSA and in contrast to all other compounds tested, remained bound to infected erythrocytes after washing and continued to inhibit binding. Both carrageenans and CS10 inhibited adhesion to placental tissue. Although highly sulfated dextran sulfate can inhibit CSA-mediated adhesion to CHO cells, this polysaccharide amplified adhesion to placental tissue severalfold, demonstrating the importance of evaluating inhibitory compounds in systems as close to in vivo as possible. Interestingly, and in contrast to all other compounds tested, which had a random distribution of sulfate groups, CS10 exhibited a clustered sulfate pattern along the polymer chain, similar to that of the undersulfated placental CSA preferred by placental-tissue-binding infected erythrocytes. Therefore, the specific antiadhesive capacity observed here seems to depend not only on the degree of charge and sulfation but also on a particular pattern of sulfation.

* Corresponding author. Mailing address: Clinical Tropical Medicine Laboratory, Infectious Diseases and Immunology Division, Queensland Institute of Medical Research, Herston, Queensland, Australia 4029. Phone: 61 (0) 7 3845 3725. Fax: 61 (0) 7 3845 3507. E-mail: kathyA{at}qimr.edu.au.

Editor: W. A. Petri, Jr.

Infection and Immunity, July 2005, p. 4288-4294, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4288-4294.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Beeson, J. G., Andrews, K. T., Boyle, M., Duffy, M. F., Choong, E. K., Byrne, T. J., Chesson, J. M., Lawson, A. M., Chai, W. (2007). Structural Basis for Binding of Plasmodium falciparum Erythrocyte Membrane Protein 1 to Chondroitin Sulfate and Placental Tissue and the Influence of Protein Polymorphisms on Binding Specificity. J. Biol. Chem. 282: 22426-22436 [Abstract] [Full Text]  
  • Adams, Y., Freeman, C., Schwartz-Albiez, R., Ferro, V., Parish, C. R., Andrews, K. T. (2006). Inhibition of Plasmodium falciparum Growth In Vitro and Adhesion to Chondroitin-4-Sulfate by the Heparan Sulfate Mimetic PI-88 and Other Sulfated Oligosaccharides.. Antimicrob. Agents Chemother. 50: 2850-2852 [Abstract] [Full Text]  


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