title: Human monocyte-endothelial cell interaction induces synthesis of granulocyte-macrophage colony-stimulating factor.
abstract: BACKGROUND
  Adhesion of monocytes to the endothelium is an initial step in the early stages of atherosclerosis and inflammation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates a range of functional activities of monocytes, including regulation of monocyte adhesion and induction of cytokine production. We investigated in this study whether CM-CSF synthesis was induced by the direct cell-to-cell interaction between human monocytes and human umbilical vein endothelial cells (ECs).
  
  
  RESULTS
  The expressions of GM-CSF mRNA and protein were analyzed by Northern blotting and ELISA, respectively. Coculture of monocytes and ECs induced the high levels of GM-CSF mRNA expression, whereas culture of ECs or monocytes alone or coculture of neutrophils with ECs induced no GM-CSF mRNA expression. A large amount of GM-CSF was secreted into the supernatant upon coculture of monocytes with ECs. The supernatant from the coculture markedly stimulated 02- release in neutrophils, and this effect was significantly inhibited by anti-GM-CSF antibody (Ab). Immunohistochemistry and in situ hybridization revealed that GM-CSF protein and mRNA were clearly detectable in both ECs and monocytes adhered to ECs but not in nonadherent monocytes. The GM-CSF production by the coculture was markedly inhibited by genistein and partially inhibited by Abs against interleukin-1 and tumor necrosis factor-alpha.
  
  
  CONCLUSIONS
  The present results indicate that GM-CSF is produced by direct interaction between monocytes and ECs and suggest that GM-CSF produced locally by monocyte-EC adhesive interaction plays an important role in the pathogenesis of atherosclerosis and inflammation by modulating monocyte/macrophage functions in vivo.
authors.affiliation: Department of Cardiology, Jichi Medical School, Togichi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Kitagawa
authors.forename: J I
authors.initials: JI
authors.lastname: Masuyama
authors.forename: U
authors.initials: U
authors.lastname: Ikeda
authors.forename: T
authors.initials: T
authors.lastname: Kasahara
authors.forename: Y I
authors.initials: YI
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Furukawa
authors.forename: S
authors.initials: S
authors.lastname: Kano
authors.forename: K
authors.initials: K
authors.lastname: Shimada
mesh_terms: D000328:Adult; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor