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Chondroitin sulfate A (CSA) is an important receptor for Plasmodium falciparum-infected erythrocytes in the placenta. To study the molecular interaction between parasitized erythrocytes (PE) to CSA, we performed in vitro cytoadherence inhibition assays of PE infected with wild and laboratory isolates of P. falciparum to CSA using various glycosaminoglycans (GAGs). Marked decrease in PE adhesion to immobilized CSA and CSA-expressed cells was achieved with soluble chondroitin sulfate D (CSD) and chondroitin sulfate E (CSE) at low concentrations. The effect was dose dependent with the degree of inhibition exceeded that of soluble CSA in certain clinical isolates. The results suggested the influence of oversulfation of CS variant chains on PE adherence to CSA. Interestingly, PE of the tested wild isolates could adhere to immobilized CSD and CSE at different levels while PE of CSA-selected laboratory lines could not. Partial inhibitory activity was observed when chondroitin sulfate C (CSC), chondroitin sulfate B (CSB), and polyolpolysulfate were used even at high concentrations. Keratan sulfate, colominic acid, and Suramine were unable to inhibit PE adherence. Taken together, the results confirm that the 4-sulfate amino sugar moiety, as well as the basic disaccharide structure of N-acetylgalactosamine linked to glucuronic acid, may influence the degree of this molecular interaction. However, other sulfation patterns that could influence the interaction could not be overlooked, as in the case of CSD which contains 2-O-sulfation at glucuronic acid. Studies using pentosan polysulfate, an oversulfated molecule with a xylan backbone, as an inhibitor also showed a reduction of PE adherence of most isolates tested. Thus, only the sulfate content and pattern of this molecule could affect the adhesive interactions. In addition, difference in capacity of low molecular weight heparins to inhibit CSA-mediated PE cytoadherence of clinical isolates was also observed, thereby providing evidence on the heterogeneity in cytoadherence characteristics of maternal parasite isolates as well as their therapeutic potentials.
Received June 12, 2003. Accepted for publication October 17, 2003.
Acknowledgments: We thank Professor N. J. White and his colleagues for their assistance on the field trip to Mae Sot, Tak, and Sumalee Kamchonwongpaisan for her excellent mathematical and statistical advice, including the determination of 50% inhibitory concentrations. We also express our sincere appreciation to Maurice Broughton for suggestions during manuscript preparation.
Financial support: This work was supported by the Thailand Research Fund (TRF). Sansanee C. Chaiyaroj is a TRF scholar. Sujittra Chaisavaneeyakorn is supported by the Medical Scholars Program of Mahidol University. François Nosten and Rose McGready are supported by the Wellcome Trust of Great Britain.
Authors’ addresses: Sujittra Chaisavaneeyakorn, Pornpimon Angkasekwinai, and Sansanee C. Chaiyaroj, Department of Microbiology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand, Telephone: 66-2-201-5689, Fax: 66-2-644-5411, E-mail: scscy{at}mahidol.ac.th. Prachya Kongtawelert, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand, Telephone: 66-1-784-6907. Alan Brockman and François Nosten, Shoklo Malaria Research Unit, Intarakiri Road, Mae Sot, Tak 63110, Thailand, Telephone and Fax: 66-55-531-531.
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