Published online before print April 13, 2007

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(American Journal of Pathology. 2007;170:1989-2000.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.061238

Chondroitin Sulfate Proteoglycan but Not Hyaluronic Acid Is the Receptor for the Adherence of Plasmodium falciparum-Infected Erythrocytes in Human Placenta, and Infected Red Blood Cell Adherence Up-Regulates the Receptor Expression

Arivalagan Muthusamy^*, Rajeshwara N. Achur^*, Manojkumar Valiyaveettil^*, John J. Botti, Diane W. Taylor, Rose F. Leke^¶ and D. Channe Gowda^*

From the Departments of Biochemistry and Molecular Biology^* and Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania; the Departments of Biochemistry and Molecular Biology and Biology, Georgetown University, Washington, District of Columbia; and the Faculty of Medicine and Biomedical Research,^¶ University of Yaounde, Yaounde, Cameroon

A low-sulfated chondroitin sulfate proteoglycan (CSPG) has been shown to be the receptor for the adherence of Plasmodium falciparum-infected red blood cells (IRBCs) in human placenta. Recently, hyaluronic acid (HA) has been suggested as an additional receptor even though IRBC binding to HA and the presence of HA at locations where IRBCs adhere in the placenta have not been established. In this study, we investigated whether HA is also a receptor for IRBC binding. IRBCs from infected placentas as well as those from different laboratory strains could bind to CSPG but not to HA. In a cell depletion assay, IRBCs from infected placentas could bind quantitatively to CSPG. Although CSPG is present both in the intervillous space and on the syncytiotrophoblast surface, HA is absent in these locations. These data conclusively demonstrate that CSPG, but not HA, is a receptor for IRBC adherence in the placenta. Our data also show, for the first time, that the IRBC-binding CSPG in the placenta is of fetal origin and that, in P. falciparum-infected placentas, the CSPG level is significantly increased, which could exacerbate IRBC adherence and placental pathogenesis. These results have important implications for the development of anti-IRBC adhesion-based vaccine for pregnancy-associated malaria.