Cerebral malaria is a fatal complication of infection by Plasmodium falciparum in man. The neurological symptoms that characterize this form of malarial disease are accompanied by the adhesion of infected erythrocytes to the vasculature of the brain. To study this phenomenon in vivo, an acute phase severe combined immunodeficiency (SCID) mouse model was developed in which sequestration of P. falciparum-infected human erythrocytes took place. During acute cerebral malaria in humans, the expression of intercellular adhesion molecule-1 (ICAM-1) is induced in vascular endothelium by inflammatory reactions. Acute phase ICAM-1 expression can also be obtained in SCID mice. The endothelium of the midbrain region was the most responsive to such inflammatory stimulus. It is noteworthy that the reticular formation in the midbrain controls the level of consciousness, and loss of consciousness is a symptom of cerebral malaria. We found that infected human erythrocytes were retained 24 times more than normal erythrocytes in ICAM-1-positive mouse brain. Sequestration to the brain was reduced by anti-ICAM-1 antibodies. These in vivo results were confirmed by the binding of P. falciparum-infected erythrocytes to the ICAM-1-positive endothelium in tissue sections of mouse brain. We conclude that the SCID mouse serves as a versatile in vivo model that allows the study of P. falciparum-infected erythrocyte adhesion as it occurs in human cerebral malaria. Upregulation of ICAM-1 expression in the region of the midbrain correlates with increased retention of malaria-infected erythrocytes and with the symptoms of cerebral malaria.
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1 September 1995
Article|
September 01 1995
In vivo sequestration of Plasmodium falciparum-infected human erythrocytes: a severe combined immunodeficiency mouse model for cerebral malaria.
K Willimann,
K Willimann
Department of Medical Parasitology, Swiss Tropical Institute, Basel.
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H Matile,
H Matile
Department of Medical Parasitology, Swiss Tropical Institute, Basel.
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N A Weiss,
N A Weiss
Department of Medical Parasitology, Swiss Tropical Institute, Basel.
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B A Imhof
B A Imhof
Department of Medical Parasitology, Swiss Tropical Institute, Basel.
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K Willimann
Department of Medical Parasitology, Swiss Tropical Institute, Basel.
H Matile
Department of Medical Parasitology, Swiss Tropical Institute, Basel.
N A Weiss
Department of Medical Parasitology, Swiss Tropical Institute, Basel.
B A Imhof
Department of Medical Parasitology, Swiss Tropical Institute, Basel.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 182 (3): 643–653.
Citation
K Willimann, H Matile, N A Weiss, B A Imhof; In vivo sequestration of Plasmodium falciparum-infected human erythrocytes: a severe combined immunodeficiency mouse model for cerebral malaria.. J Exp Med 1 September 1995; 182 (3): 643–653. doi: https://doi.org/10.1084/jem.182.3.643
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