The clinical complications associated with severe and cerebral malaria occur as a result of the intravascular mechanical obstruction of erythrocytes infected with the asexual stages of the parasite, Plasmodium falciparum. We now report that a primary P. falciparum-infected erythrocyte (parasitized red blood cell [PRBC]) isolate from a patient with severe complicated malaria binds to cytokine-induced human vascular endothelial cells, and that this adhesion is in part mediated by endothelial leukocyte adhesion molecule 1 (ELAM-1) and vascular cell adhesion molecule 1 (VCAM-1). PRBC binding to tumor necrosis factor alpha (TNF-alpha)-activated human vascular endothelial cells is partially inhibited by antibodies to ELAM-1 and ICAM-1 and the inhibitory effects of these antibodies is additive. PRBCs selected in vitro by sequential panning on purified adhesion molecules bind concurrently to recombinant soluble ELAM-1 and VCAM-1, and to two previously identified endothelial cell receptors for PRBCs, ICAM-1, and CD36. Post-mortem brain tissue from patients who died from cerebral malaria expressed multiple cell adhesion molecules including ELAM-1 and VCAM-1 on cerebral microvascular endothelium not expressed in brains of individuals who died from other causes. These results ascribe novel pathological functions for both ELAM-1 and VCAM-1 and may help delineate alternative adhesion pathways PRBCs use to modify malaria pathology.
Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1.
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C F Ockenhouse, T Tegoshi, Y Maeno, C Benjamin, M Ho, K E Kan, Y Thway, K Win, M Aikawa, R R Lobb; Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1.. J Exp Med 1 October 1992; 176 (4): 1183–1189. doi: https://doi.org/10.1084/jem.176.4.1183
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