title: Association of mast cell-derived VEGF and proteases in Dengue shock syndrome.
abstract: BACKGROUND
  Recent in-vitro studies have suggested that mast cells are involved in Dengue virus infection. To clarify the role of mast cells in the development of clinical Dengue fever, we compared the plasma levels of several mast cell-derived mediators (vascular endothelial cell growth factor [VEGF], soluble VEGF receptors [sVEGFRs], tryptase, and chymase) and -related cytokines (IL-4, -9, and -17) between patients with differing severity of Dengue fever and healthy controls.
  
  
  RESULTS
  The study was performed at Children's Hospital No. 2, Ho Chi Minh City, and Vinh Long Province Hospital, Vietnam from 2002 to 2005. Study patients included 103 with Dengue fever (DF), Dengue hemorrhagic fever (DHF), and Dengue shock syndrome (DSS), as diagnosed by the World Health Organization criteria. There were 189 healthy subjects, and 19 febrile illness patients of the same Kinh ethnicity. The levels of mast cell-derived mediators and -related cytokines in plasma were measured by ELISA. VEGF and sVEGFR-1 levels were significantly increased in DHF and DSS compared with those of DF and controls, whereas sVEGFR-2 levels were significantly decreased in DHF and DSS. Significant increases in tryptase and chymase levels, which were accompanied by high IL-9 and -17 concentrations, were detected in DHF and DSS patients. By day 4 of admission, VEGF, sVEGFRs, and proteases levels had returned to similar levels as DF and controls. In-vitro VEGF production by mast cells was examined in KU812 and HMC-1 cells, and was found to be highest when the cells were inoculated with Dengue virus and human Dengue virus-immune serum in the presence of IL-9.
  
  
  CONCLUSIONS
  As mast cells are an important source of VEGF, tryptase, and chymase, our findings suggest that mast cell activation and mast cell-derived mediators participate in the development of DHF. The two proteases, particularly chymase, might serve as good predictive markers of Dengue disease severity.
authors.affiliation: Division of Infectious Genetics, Institute of Medical Science, University of Tokyo, Tokyo, Japan. furuta@ims.u-tokyo.ac.jp
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
authors.forename: Lyre Anni
authors.initials: LA
authors.lastname: Murao
authors.forename: Nguyen Thi Phuong
authors.initials: NT
authors.lastname: Lan
authors.forename: Nguyen Tien
authors.initials: NT
authors.lastname: Huy
authors.forename: Vu Thi Que
authors.initials: VT
authors.lastname: Huong
authors.forename: Tran Thi
authors.initials: TT
authors.lastname: Thuy
authors.forename: Vo Dinh
authors.initials: VD
authors.lastname: Tham
authors.forename: Cao Thi Phi
authors.initials: CT
authors.lastname: Nga
authors.forename: Tran Thi Ngoc
authors.initials: TT
authors.lastname: Ha
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Ohmoto
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Kouichi
authors.initials: K
authors.lastname: Morita
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirayama
authors.forename: Naohiro
authors.initials: N
authors.lastname: Watanabe
mesh_terms: D000293:Adolescent; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D053818:Chymases / Q000097:blood*; D003716:Dengue Virus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology*; D019595:Severe Dengue / Q000276:immunology* / Q000473:pathology; D012720:Severity of Illness Index; D053802:Tryptases / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D014744:Vietnam
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D053818:Chymases; D053802:Tryptases