GLYCOBIOLOGY AND EXTRACELLULAR MATRICES
The Structural Motif in Chondroitin Sulfate for Adhesion ofPlasmodium falciparum-infected Erythrocytes Comprises Disaccharide Units of 4-O-Sulfated and Non-sulfated N-Acetylgalactosamine Linked to Glucuronic Acid*

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An important characteristic of malaria parasitePlasmodium falciparum-infected red blood cells (IRBCs) is their ability to adhere to host endothelial cells and accumulate in various organs. Sequestration of IRBCs in the placenta, associated with excess perinatal and maternal mortality, is mediated in part by adhesion of parasites to the glycosaminoglycan chondroitin sulfate A (CSA) present on syncytiotrophoblasts lining the placental blood spaces. To define key structural features for parasite interactions, we isolated from CSA oligosaccharide fractions and established by electrospray mass spectrometry and high performance liquid chromatography disaccharide composition analysis their differing chain length, sulfate content, and sulfation pattern. Testing these defined oligosaccharide fragments for their ability to inhibit IRBC adhesion to immobilized CSA revealed the importance of non-sulfated disaccharide units in combination with 4-O-sulfated disaccharides for interaction with IRBCs. Selective removal of 6-O-sulfates from oligo- and polysaccharides to increase the proportion of non-sulfated disaccharides enhanced activity, indicating that 6-O-sulfation interferes with the interaction of CSA with IRBCs. Dodecasaccharides with four or five 4-O-sulfated and two or one non-sulfated disaccharide units, respectively, comprise the minimum chain length for effective interaction with IRBCs. Comparison of the activities of CSA and CSB oligo- and polysaccharides with a similar sulfation pattern and content achieved from partial desulfation demonstrated that glucuronic acid rather than iduronic acid residues are important for IRBC binding.

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Published, JBC Papers in Press, April 15, 2002, DOI 10.1074/jbc.M111401200

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The Glycosciences Laboratory is supported by United Kingdom Medical Research Council Program Grant G9601454.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by grants from the National Health and Medical Research Council of Australia and a Cottrell Research Fellowship of the Royal Australasian College of Physicians.