Regulation of endothelial cell adhesion molecule expression in an experimental model of cerebral malaria.
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.
Bauer
Phillipe R
PR
Departments of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Van Der Heyde
Henri C
HC
Sun
Guang
G
Specian
Robert D
RD
Granger
D Neil
DN
D000818:Animals; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D016207:Cytokines / Q000502:physiology; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016779:Malaria, Cerebral / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000378:metabolism; D010962:Plasmodium berghei / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D014018:Tissue Distribution; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1