[Plasmodium falciparum and chondroitin-4-sulfate: the new key couple in sequestration].
Some complications of Plasmodium falciparum infection such as cerebral malaria and pregnancy-associated malaria may be partially due to cytoadherence of erythrocytes infected by mature parasites on microvascular endothelial cells or placental syncytiotrophoblasts. Recently a new cytoadherence receptor, chondroitin-4-sulphate (CSA), was identified first on endothelial cells in primates and then on CHO cells and purified receptors. Further study has implicated CSA in cytoadherence of infected red blood cells to syncytiotrophoblasts in human placenta and Saimiri sciureus monkeys. In solution the minimal size for full inhibitory effect is approximately 9 kDa. Injection of CSA in Plasmodium falciparum-infected Saimiri monkeys resulted in specific release of sequestered erythrocytes infected by mature parasites. An added interest of these findings is that CSA, a glycosaminoglycan, is already in clinical use for treatment of degenerative joint disease. Current data on the parasite ligand for CSA indicates that it is not co-expressed with other cytoadherence ligands and that its binding activity decreases as the parasite matures from the 20th to 40th hour of the cycle. Since one or more var genes encoding the CSA ligand have been identified, it is likely that peptides will be obtained quickly and used either for direct inhibition of cytoadherence on CSA or for development of an anti-sequestration vaccine.
Pouvelle
B
B
Laboratoire de Parasitologie Expérimentale, Faculté de Médecine Aix-Marseille II, France. ygypaly@imaginet.fr
Fusai
T
T
Gysin
J
J
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D002809:Chondroitin Sulfates / Q000378:metabolism*; D006224:Cricetinae; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D006801:Humans; D016779:Malaria, Cerebral / Q000097:blood; D010963:Plasmodium falciparum / Q000378:metabolism*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000097:blood; D012453:Saimiri
D002809:Chondroitin Sulfates