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Women are susceptible to malaria pathogenesis when they became pregnant, although they have previously acquired immunity against developing severe malaria. Sequestration of parasitized red blood cells in the placenta appears to be crucial to the development of complications of malaria in pregnancy. Binding of Plasmodium falciparum-infected red blood cells (IRBC) to the human placenta has been shown to be mediated by chondroitin 4-sulfate(C4S). However, the chondroitin sulfate proteoglycans (CSPGs) involved in this process have not been identified. The first paper introduced here [Achur, R.N., et al. (2000) J. Biol. Chem. 275, 40344-40356], reports on the purification and characterization of human placental CSPGs, and binding activity of IRBC to the purified placental CSPGs. Proteoglycans of intervillous spaces were extracted from the human placenta tissues with ice-cold PBS by gentle scraping. Cell-associated proteoglycans were extracted from PBS-washed placenta with a buffer containing 0.5% Triton X-100. Finally, proteoglycans of the fibrous tissues were extracted from the detergent-treated placenta with a buffer containing 0.5% Triton X-100 and 6M urea. Proteoglycans of intervillous spaces were separated into two fractions bearing low sulfated C4S that contained 2% or 8% of 4-sulfated disaccharide units. Cell-associated proteoglycans were mixtures of CSPG and heparan sulfate proteoglycan. CSPG fractions obtained after digestion with heparitinase contained partially sulfated chondroitin sulfate (the degree of sulfation was about 50% and the ratio of 6-sulfate/4sulfate was about 0.5). Proteoglycans of the fibrous tissues were separated into two fractions of 800 kDa and 150 kDa. Both fractions contained fully sulfated chondroitin sulfate/dermatan sulfate (the ratio of 6-sulfate/4-sulfate was about 0.5 for 800 kDa and about 0.25 for 150 kDa). Of the three fractions, proteoglycans of intervillous spaces containing low sulfated C4S showed the highest IRBC binding capacity, whereas proteoglycans of the fibrous tissues containing fully sulfated chondroitin sulfate/dermatan sulfate showed the lowest binding activity. The IRBC adhesion to the proteoglycans of intervillous spaces was completely abolished upon incubation with chondroitinase ABC or testicular hyaluronidase, but was not affected by digestion with S. hyalurolyticus hyaluronidase which was highly specific to HA, or heparitinase. マ ラ リア の多 発 地 帯 で は 以前 に免 疫 を獲 得 した に もか か わ

trends in glycoscience and glycotechnology

Proteoglycans of the Human Placenta Bearing Low Sulfated Chondroitin 4-Sulfate Mediate the Adherence of Plasmodium falciparum-Infected Erythrocytes to the Placenta