Characterisation of the chondroitin sulphate of Saimiri brain microvascular endothelial cells involved in Plasmodium falciparum cytoadhesion

Cytoadhesion of Plasmodium falciparum-infected erythrocytes (IRBC) to chond roitin-4-sulphate (CSA) is inhibited by soluble CSA in vitro on Saimiri bra in microvascular endothelial cells (SBEC) and in vivo in P. falciparum-infe cted Saimiri monkeys. We tested whether the SBEC model was appropriate for studying CSA-binding IRBC using four cell lines. All SBEC expressed a chond roitin sulphate (CS), with a composition of CSA. The mean sizes of these CS A were 20.5, 22, 23, 32.5 and 36 kDa for SBEC 3A and C2, CHO, SBEC 1D and 1 7, respectively. We found that cytoadhesion of the Palo-Alto (FUP)1 CSA-bin ding phenotype, selected by panning on SBEC 17, was specifically inhibited in a dose-dependent manner by all the purified CSA. The extent of inhibitio n depended on the cellular origin of the tested CSA. SBEC 17 CSA was 33 tim es more efficient than CHO-CSA and 21 times more efficient than the 50 kDa commercial bovine trachaea CSA. Dynabeads coated with a total extract of SB EC 1D CS-proteoglycans interacted with CSA- but not with CD36- or ICAM-1-bi nding IRBC. These Dynabeads also interacted specifically with the PfEMP1 DB L-3 domain, on the surface of CHO transfectants, but not with the CIDR-1 do main. Thrombomodulin was involved in IRBC adhesion to all SBEC whereas CD44 was only expressed by SBEC 1D and 17. These two CSA-proteoglycans have als o been detected at the surface of human endothelial cells. Thus: the two ho mologous models, SBEC/Saimiri sciureus, are useful and reliable tools for t he evaluation of new anti-CSA adhesion treatments and anti-disease vaccines for pregnant women. (C) 2000 Elsevier Science B.V. All rights reserved.