Proinflammatory factors present in sera from patients with acute dengue infection induce activation and apoptosis of human microvascular endothelial cells: possible role of TNF-alpha in endothelial cell damage in dengue.
There is evidence that severe dengue disease is associated with alterations of the microvascular endothelium. We examined the hypothesis that activation and damage of microvascular endothelial cells (EC) could be induced by inflammatory mediators present in dengue patient's sera. We cultured human microvascular EC (HMEC-1) in vitro with sera from patients with acute dengue infection. Sera from patients with acute dengue induced an increase in ICAM-1 expression on HMEC-1. This effect was greater with samples from the acute febrile phase than with samples from the convalescent phase of the disease. Acute dengue sera had elevated levels of TNF-alpha and the endothelial activating effect of acute dengue sera was inhibited up to 80% by pre-treatment with monoclonal antibodies against TNF-alpha. Furthermore, acute dengue sera induced apoptosis in HMEC-1. These findings support the pathophysiologic significance of microvascular EC and serum inflammatory mediators in dengue.
Cardier
José E
JE
Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado Postal: 21827, Caracas 1020A, Venezuela. jcardier@ivic.ve
Mariño
Eliana
E
Romano
Egidio
E
Taylor
Peter
P
Liprandi
Ferdinando
F
Bosch
Norma
N
Rothman
Alan L
AL
D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D003715:Dengue / Q000276:immunology / Q000378:metabolism*; D042783:Endothelial Cells / Q000821:virology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008833:Microcirculation; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1