Upregulation of intercellular adhesion molecule-1 expression on human endothelial cells by tumour necrosis factor-alpha in an in vitro model of the blood-brain barrier.
Adhesion molecules on the endothelial surface of the blood-brain barrier (BBB) play an important role in the pathogenesis of many encephalopathies, including multiple sclerosis (MS) and cerebral malaria (CM). The expression of four surface molecules of relevance to MS and CM on the immortalized human umbilical vein endothelial cell line, ECV304, was investigated using immunofluorescence flow cytometry. We found that ECV304 cells express intercellular adhesion molecule-1 (ICAM-1) and low levels of CD36, but not vascular cell adhesion molecule-1 (VCAM-1) or E-selectin. This expression pattern was unaltered on ECV304 cells which were co-cultured with C6 glioma cells; conditions under which the endothelial cells display enhanced barrier formation. Tumour necrosis factor-alpha (TNF-alpha), which is elevated in MS and CM, decreased the integrity of the barrier in co-cultured endothelial cells and upregulated the expression of ICAM-1 nine-fold. The significance of elevated ICAM-1 expression in relation to the binding of parasitised erythrocytes at the BBB in CM is discussed.
Dobbie
M S
MS
Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Hurst
R D
RD
Klein
N J
NJ
Surtees
R A
RA
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D018955:CD36 Antigens / Q000032:analysis; D002460:Cell Line; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D018955:CD36 Antigens; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1