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 Pl asmodium falciparum cytoadherence receptor present on Saimiri brain mi crovascular and human lung endothelial cells. Materials and Methods: T o specifically study chondroitin-4-sulfate-mediated cytoadherence, a p arasite 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 lin e to be unique for its expression of CSA-proteoglycans, namely CD44 an d thrombomodulin, in the absence of CD36 and ICAM-1. Results: The sele cted parasite population was used to monitor cytoadherence inhibition/ dissociating activities in Saimiri sera collected at different times a fter intramuscular injection of 50 mg CSA/kg of body weight. Serum inh ibitory activity was detectable 30 min after injection and persisted f or 8 hr. Furthermore, when chondroitin-A-sulfate was injected into mon keys infected with Palo-Alto (FUP) 1 P, faliparum, erythrocytes contai ning P. falciparum mature forms were released into the circulation. Th e cytoadherence phenotype of circulating infected red blood cells (IRB C) was determined before and 8 hr after inoculation of CSA. Before ino culation, 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 cytoadh erence of parasitized erythrocytes.