Supernatants from dengue virus type-2 infected macrophages induce permeability changes in endothelial cell monolayers

• Published in: Journal of medical virology Vol. 69; no. 4; pp. 521 - 528
• Main Authors: Carr, Jillian M., Hocking, Helen, Bunting, Karen, Wright, Peter J., Davidson, Andrew, Gamble, Jennifer, Burrell, Christopher J., Li, Peng
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.04.2003; Wiley-Liss
• Subjects: Biological and medical sciences; capillary leakage; Cell Membrane Permeability; Cells, Cultured; dengue haemorrhagic fever; Dengue Virus - physiology; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; flavivirus; Fundamental and applied biological sciences. Psychology; human umbilical vein endothelial cell; Humans; Macrophages - virology; Microbiology; Monocytes - virology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Tumor Necrosis Factor-alpha - metabolism; Umbilical Veins; Virology; Endothelial cell; Dengue hemorrhagic fever; Cell permeability; Pathogenesis; Dengue; Dengue virus 2; Flavivirus; Host virus relation; Infection; Virus; Viral disease; Dengue group virus; Arbovirus disease; Flaviviridae; Macrophage
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.10340

The ability of dengue virus‐infected human monocyte‐derived macrophages to induce permeability changes in primary human umbilical vein endothelial cells was investigated. Supernatants from dengue virus type 2‐infected monocyte‐derived macrophages increased permeability in human umbilical vein endothelial cell monolayers without inducing endothelial cell infection. Production of permeabilising activity from monocyte‐derived macrophages occurred after the peak of progeny virus release. TNF‐α, a known inducer of endothelial cell permeability, was released from dengue virus infected monocyte‐derived macrophages but its release did not coincide with release of endothelial cell permeabilising activity. Permeability induction was enhanced by pre‐incubation with supernatants from infected monocyte‐derived macrophages harvested at the time of peak release of TNF‐α and infectious virus. Thus, supernatants from dengue virus‐infected monocyte‐derived macrophages contain factors that increase human umbilical vein endothelial cell permeability, but this is not accompanied by endothelial cell infection or directly correlated with release of dengue virus or TNF‐α from monocyte‐derived macrophages. This model system can be used for further in vitro analysis of mechanisms that may relate to capillary leakage and the development of dengue haemorrhagic fever/dengue shock syndrome. J. Med. Virol. 69:521–528, 2003. © 2003 Wiley‐Liss, Inc.