Characterization of proteoglycans of human placenta and identification of unique chondroitin sulfate proteoglycans of the intervillous spaces that mediate the adherence of Plasmodium falciparum-infected erythrocytes to the placenta

In pregnant women infected with Plasmodium falciparum, the infected red blo od cells (IRBCs) selectively accumulate in the intervillous spaces of place nta, leading to poor fetal outcome and severe health complications in the m other. Although chondroitin 4-sulfate is known to mediate IRBC adherence to placenta, the natural receptor has not been identified. In the present stu dy, the chondroitin sulfate proteoglycans (CSPGs) of human placenta were pu rified and structurally characterized, and adherence of IRBCs to these CSPG s investigated. The data indicate that the placenta contains three distinct types of CSPGs: significant quantities of uniquely low sulfated, extracell ular CSPGs localized in the intervillous spaces, minor amounts of two cell- associated CSPGs, and major amounts of dermatan sulfate-like CSPGs of the f ibrous tissue. Of the various CSPGs isolated from the placenta, the low sul fated CSPGs of the intervillous spaces most efficiently bind IRBCs. Based o n IRBC adherence capacities and localization patterns of various CSPGs, we conclude that the CSPGs of the intervillous spaces are the receptors for pl acental IRBC adherence. The identification and characterization of these CS PGs provide a valuable tool for understanding the precise molecular interac tions involved in placental IRBC adherence and for the development of thera peutic strategies for maternal malaria. In the accompanying paper we report the structural requirements for the IRBC adherence.