Valiyaveettil Manojkumar, Achur Rajeshwara N, Muthusamy Arivalagan, Gowda D Channe
Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Mol Biochem Parasitol. 2004 Mar;134(1):115-26. doi: 10.1016/j.molbiopara.2003.11.009.
Infection with Plasmodium falciparum during pregnancy leads to chondroitin 4-sulfate-mediated adhesion of the infected red blood cells (IRBCs) in the placenta, causing severe health complications to fetus and the mother. The IRBCs are also frequently found in low density in the umbilical cord of infected placentas. In this study, the CSPGs of umbilical vein and arteries were purified, characterized, and their localization and IRBC-binding abilities were studied. While a versican type CSPG was found both in the vein and arteries, a serglycin type CSPG was present exclusively in the vein. The CSPGs were present at significant level on the endothelial surface of the umbilical vein but not on that of arteries. Although the purified versican and serglycin type CSPGs could bind IRBCs, their binding abilities were significantly less compared to the low sulfated CSPGs of the placenta because of the predominance of 6-sulfated disaccharide moieties in the CS chains. Therefore, IRBCs were unable to bind efficiently onto the umbilical cord endothelial surface. Unexpectedly, however, the IRBCs adhered densely in the blood vessels of fetal villi in the placental tissue sections and sparingly in the blood spaces of the umbilical cord vein, presumably because the CSPG that can efficiently bind IRBCs is present at high levels in the fetal blood vessels and at very low levels in the umbilical cord blood vessels. Since the C4S-adherent IRBCs that enter the fetal blood vessels cannot adhere to the cord endothelial surface and parasites cannot efficiently grow due to fetal hemoglobin toxicity and protection by maternal antibodies, transplacental infection may be quickly cleared without clinical episodes.
孕期感染恶性疟原虫会导致感染的红细胞（IRBCs）通过硫酸软骨素4介导黏附于胎盘，给胎儿和母亲带来严重的健康并发症。在受感染胎盘的脐带中也经常发现低密度的IRBCs。在本研究中，对脐静脉和动脉的硫酸软骨素蛋白聚糖（CSPGs）进行了纯化、表征，并研究了它们的定位和IRBC结合能力。虽然在静脉和动脉中都发现了多功能蛋白聚糖CSPG，但丝甘蛋白聚糖CSPG仅存在于静脉中。CSPGs在脐静脉内皮表面大量存在，而在动脉内皮表面则不存在。尽管纯化的多功能蛋白聚糖和丝甘蛋白聚糖CSPG能够结合IRBCs，但由于硫酸软骨素（CS）链中6 - 硫酸化二糖部分占主导，它们的结合能力与胎盘的低硫酸化CSPGs相比显著降低。因此，IRBCs无法有效地黏附在脐带内皮表面。然而，出乎意料的是，IRBCs在胎盘组织切片中胎儿绒毛的血管中密集黏附，而在脐静脉血窦中黏附较少，推测是因为能够有效结合IRBCs的CSPG在胎儿血管中含量高，而在脐带血管中含量极低。由于进入胎儿血管的C4S黏附IRBCs无法黏附在脐带内皮表面，并且由于胎儿血红蛋白毒性和母体抗体的保护，寄生虫无法有效生长，经胎盘感染可能会在无临床发作的情况下迅速清除。
