MCP-1, a highly expressed chemokine in dengue haemorrhagic fever/dengue shock syndrome patients, may cause permeability change, possibly through reduced tight junctions of vascular endothelium cells.
Vascular leakage, one hallmark of dengue haemorrhagic fever (DHF) and dengue shock syndrome, has been linked to the mediators secreted from cells in the circulatory system. In this study, extremely high expression levels of monocyte chemoattractant protein-1 (MCP-1) were found in the plasma of DHF patients compared with low MCP-1 expression levels in the plasma of enterovirus 71-infected patients. It was also found that MCP-1 expression was induced in dengue virus 2 (DV2)-infected monocytes and lymphocytes, but not in liver or endothelial cells. Exposing monolayers of human umbilical vein endothelial cells (HUVECs) to recombinant human MCP-1 (rhMCP-1) or to the culture supernatant of DV2-infected human monocytes increased the vascular permeability of the cells. MCP-1-neutralizing monoclonal antibody only partially prevented monolayer permeability change. Consistently, the distribution of the tight junction protein ZO-1 on the cellular membranes of HUVECs was disrupted by rhMCP-1 or by the conditioned medium of DV2-infected monocytes. In summary, it was found that the increased permeability and disrupted tight junctions of human vascular endothelium cells were effected through a mechanism partially dependent on MCP-1, which was secreted by DV2-infected monocytes and lymphocytes.
Lee
Ying-Ray
YR
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 1 Da-Shue Road, Tainan 701, Taiwan.
Liu
Ming-Tao
MT
Tainan Hospital, Department of Health, Executive Yuan, Tainan, Taiwan.
Lei
Huan-Yao
HY
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 Da-Shue Road, Tainan 701, Taiwan.|Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 1 Da-Shue Road, Tainan 701, Taiwan.
Liu
Ching-Chuan
CC
Department of Pediatrics, College of Medicine, National Cheng Kung University, 1 Da-Shue Road, Tainan 701, Taiwan.
Wu
Jing-Ming
JM
Department of Pediatrics, College of Medicine, National Cheng Kung University, 1 Da-Shue Road, Tainan 701, Taiwan.
Tung
Yi-Ching
YC
Department of Clinical Laboratory, Kaohsiung Medical University, Kaohsiung City, Taiwan.
Lin
Yee-Shin
YS
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 Da-Shue Road, Tainan 701, Taiwan.
Yeh
Trai-Ming
TM
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 Da-Shue Road, Tainan 701, Taiwan.
Chen
Shun-Hua
SH
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 Da-Shue Road, Tainan 701, Taiwan.
Liu
Hsiao-Sheng
HS
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 Da-Shue Road, Tainan 701, Taiwan.
D002199:Capillary Permeability; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000502:physiology*; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000378:metabolism / Q000821:virology; D004769:Enterovirus Infections / Q000276:immunology / Q000503:physiopathology; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology; D008565:Membrane Proteins / Q000032:analysis; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D010750:Phosphoproteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019595:Severe Dengue / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D019108:Tight Junctions / Q000502:physiology / Q000648:ultrastructure; D015854:Up-Regulation; D062826:Zonula Occludens-1 Protein
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein