Supernatants from dengue virus type-2 infected macrophages induce permeability changes in endothelial cell monolayers.
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-alpha, 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-alpha 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-alpha 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.
Carr
Jillian M
JM
Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Adelaide, South Australia. jill.carr@imvs.sa.gov.au
Hocking
Helen
H
Bunting
Karen
K
Wright
Peter J
PJ
Davidson
Andrew
A
Gamble
Jennifer
J
Burrell
Christopher J
CJ
Li
Peng
P
D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003716:Dengue Virus / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D009000:Monocytes / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014471:Umbilical Veins
D014409:Tumor Necrosis Factor-alpha