Regulation of endothelial cell adhesion molecule expression in an experimental model of cerebral malaria |
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Authors: | Bauer Phillipe R Van Der Heyde Henri C Sun Guang Specian Robert D Granger D Neil |
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Affiliation: | Departments of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA. |
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Abstract: | OBJECTIVE: Plasmodium falciparum malaria in humans and animal models of this disease have revealed changes in the infected host that are consistent with a systemic inflammatory response. Although it has been proposed that endothelial cell adhesion molecules (CAM) contribute to the adhesive interactions of Plasmodium-infected erythrocytes and immune cells with vascular endothelial cells, ECAM expression has not been systematically studied in Plasmodium-infected animals. METHODS: In this study, the dual radiolabeled monoclonal antibody method was used to quantify the expression of different ECAMs (ICAM-1, VCAM-1, P-selectin, E-selectin) in different regional vascular beds of Plasmodium berghei ANKA-inffected mice (PbA), a well-recognized model of human cerebral malaria. The roles of T lymphocytes and certain cytokines (TNF-alpha, IL-12, IFN-gamma) in mediating the infection-induced expression of ICAM-1 and P-selectin were assessed by using relevant mutant mice. RESULTS: Wild-type (WT) mice exhibited highly significant increases in the expression of ICAM-1, VCAM-1, and P-selectin (but not E-selectin) in all vascular beds on the 6th day of PbA infection. The PbA-induced upregulation of ICAM-1 was significantly blunted in mice that were either deficient in IFN-alpha, IL-12 (but not TNF1b) or T lymphocytes (Rag-1 deficiency); however, these responses were tissue specific. CONCLUSIONS: These findings indicate that vascular endothelial cells in most regional circulations assume an inflammatory phenotype and that cytokines and immune cells mediate this response in a tissue-specific manner. |
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Keywords: | ICAM-1 VCAM-1 P-selectin E-selectin cerebral malaria |
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