Dengue virus infection of mast cells triggers endothelial cell activation.
Vascular perturbation is a hallmark of severe forms of dengue disease. We show here that antibody-enhanced dengue virus infection of primary human cord blood-derived mast cells (CBMCs) and the human mast cell-like line HMC-1 results in the release of factor(s) which activate human endothelial cells, as evidenced by increased expression of the adhesion molecules ICAM-1 and VCAM-1. Endothelial cell activation was prevented by pretreatment of mast cell-derived supernatants with a tumor necrosis factor (TNF)-specific blocking antibody, thus identifying TNF as the endothelial cell-activating factor. Our findings suggest that mast cells may represent an important source of TNF, promoting vascular endothelial perturbation following antibody-enhanced dengue virus infection.
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada.
Michael G
MG
Brown
Laura L
LL
Hermann
Andrew C
AC
Issekutz
Jean S
JS
Marshall
Derek
D
Rowter
Ayham
A
Al-Afif
Robert
R
Anderson
D019138:Antibodies, Blocking / Q000276:immunology; D002478:Cells, Cultured; D003716:Dengue Virus / Q000276:immunology / Q000472:pathogenicity*; D042783:Endothelial Cells / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008407:Mast Cells / Q000276:immunology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D019138:Antibodies, Blocking; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1