Human monocyte-endothelial cell interaction induces synthesis of granulocyte-macrophage colony-stimulating factor.
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.
Takahashi
M
M
Department of Cardiology, Jichi Medical School, Togichi, Japan.
Kitagawa
S
S
Masuyama
J I
JI
Ikeda
U
U
Kasahara
T
T
Takahashi
Y I
YI
Furukawa
Y
Y
Kano
S
S
Shimada
K
K
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
D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor