(Circulation. 1996;93:1185-1193.)
© 1996 American Heart Association, Inc.
Articles |
Human Monocyte–Endothelial Cell Interaction Induces Synthesis of Granulocyte-Macrophage Colony-Stimulating Factor
From the Department of Cardiology (M.T., U.I., K.S.), Division of Hemopoiesis (S. Kitagawa, Y.F.), and Departments of Clinical Immunology (J.M., S. Kano) and Medical Biology and Parasitology (T.K.), Jichi Medical School, Tochigi, and the Department of Clinical and Laboratory Medicine (Y.T.), Tohoku University School of Medicine, Miyagi, Japan.
Correspondence to Seiichi Kitagawa, MD, Division of Hemopoiesis, Institute of Hematology and Department of Medicine, Jichi Medical School, Minamikawachi-machi, Tochigi 329-04, Japan.
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 GM-CSF synthesis was induced by the direct cell-to-cell interaction between human monocytes and human umbilical vein endothelial cells (ECs).
Methods and 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 O2- 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-
.
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.
Key Words: endothelium • glycoproteins • leukocytes • atherosclerosis • immunohistochemistry
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