INDUCTION OF ADHESIVENESS IN HUMAN ENDOTHELIAL-CELLS BY PLASMODIUM-FALCIPARUM-INFECTED ERYTHROCYTES

Cytoadhesion of infected erythrocytes to endothelium plays an importan t role in the pathogenesis of Plasmodium falciparum malaria. In vitro assays of cytoadhesion have helped to identify putative host ligands, namely thrombospondin, platelet glycoprotein IV (CD36), and intercellu lar adhesion molecule-1 (CD54) as possible mediators of cytoadhesion. However, the presence of these ligands on some host cells to which inf ected erythrocytes do not adhere raises the possibility that other mol ecules or factors may be involved. In the present study, we investigat ed the effects of prolonged incubation of endothelial cells (EC) with infected erythrocytes on adhesiveness of EC. We also studied the effec ts of tumor necrosis factor (TNF), interleukin-1 (IL-1), and phorbol m yristate acetate (PMA). We found that when EC were incubated in contac t with ring-infected erythrocytes for 24 hr during which the rings dev eloped into trophozoites, adhesiveness was enhanced up to 250%. Incuba tion of EC with IL-1 or TNF for 12 hr increased adhesiveness by 50% at minimum doses of 5 U/ml and 50 U/ml, respectively, while PMA decrease d adhesiveness in a consistent and dose-dependent manner. These result s show that host EC adhesive ligands for infected erythrocytes can be induced, most notably by direct contact between the EC and infected er ythrocytes containing developing parasites. The cultured human EC used in this study lacked surface CD36 detectable by immunofluorescence as say, suggesting that CD36 is not required for endothelial adhesiveness .