ULTRASTRUCTURAL ASPECTS OF PLASMODIUM-FALCIPARUM-INFECTED ERYTHROCYTEADHERENCE TO ENDOTHELIAL-CELLS OF SAIMIRI BRAIN MICROVASCULATURE

We have recently shown that some squirrel monkeys (Saimiri sciureus) d evelop cerebral malaria when experimentally infected with asexual bloo d stage forms of different Plasmodium falciparum isolates. Since cereb ral malaria is neither an inconsistent nor predictable event, several clones of endothelial cells isolated from the squirrel monkey brain mi crovasculature have been developed. Infected red blood cell (IRBC) adh erence involved the knobs and direct membrane interactions through pse udopodes and microvilli on the Saimiri brain endothelial cell (SBEC) s urface, similar to that observed with both brain microvascular endothe lial cells from a patient who died of cerebral malaria and the rhesus monkey/P. coatneyi cerebral malaria model. The involvement of pseudopo des and microvilli increase the endothelial cell surface for the attac hment of IRBCs; however, they are already present before the SBECs are exposed to IRBCs. With some SBEC phenotypes, embedding of IRBCs into the cytoplasma membrane of the endothelial cell was observed, resultin g in an extremely close apposition of both SBEC and IRBC membranes dur ing the adherence process. Once IRBCs are adherent, particularly for t he embedding type, heterocellular communication like structures betwee n the cells become apparent. The upregulation of CD36 and intercellula r adhesion molecule-1 by soluble recombinant (sr)-tumor necrosis facto r-alpha or sr-interferon-gamma did nut modify the IRBC interactions wi th SBECs at the ultrastructural level. The study shows further that th e observed differences of IRBC adherence are due to unidentified pheno typic differences of SBECs rather than to a parasite isolate or partic ular endothelial cell receptor-associated phenomenon. Exploring P. fal ciparum IRBC cytoadherence in the squirrel monkey using a homologous p hysiologic target cell model in vitro should be useful for the evaluat ion of vaccine strategies and drugs to prevent human cerebral malaria.