BIOLOGICAL AND BIOCHEMICAL CHARACTERISTICS OF CYTOADHESION OF PLASMODIUM-FALCIPARUM-INFECTED ERYTHROCYTES TO CHONDROITIN-4-SULFATE

The cytoadhesion of Plasmodium falciparum laboratory strains and clone s to Saimiri brain microvascular endothelial cells (SBEC 17), with cho ndroitin-4-sulfate (CSA) as the only adhesion receptor, was tested. On ly one strain had significant cytoadhesion. However, CSA-specific infe cted erythrocytes (IRBCs) were detected in all strains after selection of a CSA-specific subpopulation by culturing the few adherent IRBCs. This demonstrates the lack of sensitivity of cytoadhesion microassays for detecting small quantities of CSA-specific IRBCs in cultures or fi eld isolates. Cytoadhesion to CSA is maximal at 24 h of the cycle and decreases with the onset of schizogony, reaching a minimum just before reinvasion. This fluctuation must be taken into account in comparison s of the cytoadhesion of different strains or isolates, The minimum si ze of CSA for active inhibition was 4 kDa, and a mass of 9 kDa was req uired for inhibition similar to that obtained with the 50-kDa CSA. In contrast to cytoadhesion to CSA, which is pH independent or maximal at physiological pH (depending on the target endothelial cells), adhesio n to CD36 and intercellular adhesion molecule 1 was pH dependent, requ iring acidic conditions to be maximal in all cases. Cytoadhesion to CS A may trigger the occlusion of microvessels and cause the acidosis nec essary for the other receptors to be fully efficient. If this key role in the mechanisms of sequestration were to be confirmed in vivo, prev alence studies of the CSA cytoadhesion phenotype would have to be reev aluated, because simple cytoadhesion assays do not detect CSA-specific parasites present in very low numbers, and these parasites might then be undetected in the peripheral blood but present in organs in which sequestration occurs, such as the placenta (M. Fried and P. E. Duffy, Science 272:1502-1504, 1996).