Chondroitin-4-sulfate impairs in vitro and in vivo cytoadherence of Plasmodium falciparum infected erythrocytes.
BACKGROUND
Chondroitin-4-sulfate (CSA) was recently described as a Plasmodium falciparum cytoadherence receptor present on Saimiri brain microvascular and human lung endothelial cells.


METHODS
To specifically study chondroitin-4-sulfate-mediated cytoadherence, a parasite population was selected through panning of the Palo-Alto (FUP) 1 P. falciparum isolate on monolayers of Saimiri brain microvascular endothelial cells (SBEC). Immunofluorescence showed this SBEC cell line to be unique for its expression of CSA-proteoglycans, namely CD44 and thrombomodulin, in the absence of CD36 and ICAM-1.


RESULTS
The selected parasite population was used to monitor cytoadherence inhibition/dissociating activities in Saimiri sera collected at different times after intramuscular injection of 50 mg CSA/kg of body weight. Serum inhibitory activity was detectable 30 min after injection and persisted for 8 hr. Furthermore, when chondroitin-4-sulfate was injected into monkeys infected with Palo-Alto (FUP) 1 P. falciparum, erythrocytes containing P. falciparum mature forms were released into the circulation. The cytoadherence phenotype of circulating infected red blood cells (IRBC) was determined before and 8 hr after inoculation of CSA. Before inoculation, in vitro cytoadherence of IRBCs was not inhibited by CSA. In contrast, in vitro cytoadherence of circulating infected erythrocytes obtained 8 hr after CSA inoculation was inhibited by more than 90% by CSA.


CONCLUSIONS
In the squirrel monkey model for infection with P. falciparum, chondroitin-4-sulfate impairs in vitro and in vivo cytoadherence of parasitized erythrocytes.
Pouvelle
B
B
Unité de Parasitologie Expérimentale, Institut Pasteur de Lyon, Domaine du Poirier, Lentilly, France.
Meyer
P
P
Robert
C
C
Bardel
L
L
Gysin
J
J
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000032:analysis / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000469:parasitology; D004912:Erythrocytes / Q000737:chemistry / Q000166:cytology / Q000469:parasitology*; D005260:Female; D018960:Hyaluronan Receptors / Q000032:analysis; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D010641:Phenotype; D010963:Plasmodium falciparum / Q000302:isolation & purification / Q000472:pathogenicity*; D012453:Saimiri; D018180:Thrombomodulin / Q000032:analysis
D018960:Hyaluronan Receptors; D018180:Thrombomodulin; D002809:Chondroitin Sulfates