Induction of adhesiveness in human endothelial cells by Plasmodium falciparum-infected erythrocytes.
Cytoadhesion of infected erythrocytes to endothelium plays an important 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 intercellular adhesion molecule-1 (CD54) as possible mediators of cytoadhesion. However, the presence of these ligands on some host cells to which infected erythrocytes do not adhere raises the possibility that other molecules or factors may be involved. In the present study, we investigated the effects of prolonged incubation of endothelial cells (EC) with infected erythrocytes on adhesiveness of EC. We also studied the effects of tumor necrosis factor (TNF), interleukin-1 (IL-1), and phorbol myristate acetate (PMA). We found that when EC were incubated in contact with ring-infected erythrocytes for 24 hr during which the rings developed into trophozoites, adhesiveness was enhanced up to 250%. Incubation 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 decreased adhesiveness in a consistent and dose-dependent manner. These results show that host EC adhesive ligands for infected erythrocytes can be induced, most notably by direct contact between the EC and infected erythrocytes containing developing parasites. The cultured human EC used in this study lacked surface CD36 detectable by immunofluorescence assay, suggesting that CD36 is not required for endothelial adhesiveness.
Udeinya
I J
IJ
Department of Anesthesiology, College of Medicine, Howard University, Washington, District of Columbia.
Akogyeram
C O
CO
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology* / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000469:parasitology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D010963:Plasmodium falciparum / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D008024:Ligands; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate