Peripheral blood mononuclear cells increase the permeability of dengue virus-infected endothelial cells in association with downregulation of vascular endothelial cadherin.
Plasma leakage is one of the characteristic features of dengue haemorrhagic fever. The interaction among peripheral blood mononuclear cells (PBMCs), dengue virus and endothelial cells was analysed in vitro. Human umbilical vein endothelial cells (HUVECs) were infected with dengue-2 virus (DV-2) at an m.o.i. of 0.5 p.f.u. per cell. PBMCs were added to DV-2-infected HUVECs, and transendothelial electrical resistance (TEER) and transalbumin permeability were assessed. Dengue virus infection at an m.o.i. of 0.5 p.f.u. per cell alone did not decrease the TEER, but addition of PBMCs decreased the TEER, increased the albumin permeability and induced morphological changes of HUVECs. The extent of the decrease was more profound with adherent PBMCs than with non-adherent PBMCs. The expression of vascular endothelial cadherin (VE-cadherin) was examined using real-time RT-PCR and immunofluorescence. Addition of PBMCs to DV-2-infected HUVECs decreased the levels of mRNA transcripts and cell-surface expression of VE-cadherin. The results indicate that PBMCs increased the permeability of DV-2-infected HUVECs and that the increased permeability was concomitant with morphological change and the decrease in VE-cadherin expression. The results suggest that functional impairment of the DV-2-infected HUVEC monolayer was caused by interaction with PBMCs.
Dewi
Beti Ernawati
BE
Department of Infection Biology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.|Department of Microbiology, Medical Faculty, University of Indonesia, Jalan Pegangsaan Timur no. 16, Jakarta 10320, Indonesia.|Laboratory of Vector-Borne Viruses, Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Takasaki
Tomohiko
T
Laboratory of Vector-Borne Viruses, Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Kurane
Ichiro
I
Department of Infection Biology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.|Laboratory of Vector-Borne Viruses, Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
D000328:Adult; D000418:Albumins / Q000502:physiology; D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003716:Dengue Virus / Q000472:pathogenicity*; D015536:Down-Regulation; D017097:Electric Impedance; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology / Q000821:virology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000821:virology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology / Q000821:virology; D000099152:Cadherin 5
D000418:Albumins; D015703:Antigens, CD; D015820:Cadherins; D000099152:Cadherin 5