Abstract
The reactivity of endothelial cells (ECs) to proinflammatory cytokines is critically important for the pathogenesis of vascular diseases. Here, we studied functional alterations of human ECs during culture under a confluent condition; i.e., the alterations of neutrophil-activating activity, platelet-activating factor (PAF) synthesis, and granulocyte-macrophage colony-stimulating factor (GM-CSF) production in cytokine-stimulated ECs. Human umbilical vein-derived ECs exhibited the increased activity in neutrophil activation, PAF synthesis, and GM-CSF production when stimulated by proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). The activity of cytokine-stimulated ECs to stimulate superoxide release in human neutrophils and to produce PAF declined markedly in parallel as ECs became growth-arrested during culture under a confluent condition. By contrast, GM-CSF production induced by cytokine stimulation was modestly increased, and up-regulation of intercellular adhesion molecule-1 (ICAM-1) and activation of mitogen-activated protein kinases were not altered. The neutrophil-activating activity of cytokine-stimulated ECs was dependent on PAF synthesis and GM-CSF production from ECs. These findings indicate that the reduced neutrophil-activating activity in growth-arrested ECs may be, at least in part, ascribed to down-regulation of PAF synthesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies / pharmacology
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Blotting, Western
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Cell Adhesion / drug effects
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Cell Communication / drug effects
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Cell Communication / physiology
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Cell Count
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Cell Proliferation
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Coculture Techniques
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Culture Media, Conditioned / pharmacology
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Cytokines / pharmacology*
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Endothelial Cells / drug effects*
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Endothelial Cells / metabolism
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Endothelial Cells / physiology
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Flow Cytometry
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Granulocyte-Macrophage Colony-Stimulating Factor / immunology
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Humans
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Intercellular Adhesion Molecule-1 / metabolism
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Interleukin-1beta / pharmacology
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Neutrophil Activation / physiology*
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Neutrophils / drug effects
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Neutrophils / metabolism
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Phosphorylation / drug effects
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Piperazines / pharmacology
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Platelet Activating Factor / antagonists & inhibitors
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Platelet Activating Factor / biosynthesis*
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Platelet Aggregation Inhibitors / pharmacology
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Superoxides / metabolism
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Thiazolidines / pharmacology
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Antibodies
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Culture Media, Conditioned
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Cytokines
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Interleukin-1beta
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Piperazines
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Platelet Activating Factor
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Platelet Aggregation Inhibitors
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Thiazolidines
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Tumor Necrosis Factor-alpha
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Superoxides
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Intercellular Adhesion Molecule-1
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YM 264
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Granulocyte-Macrophage Colony-Stimulating Factor
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Mitogen-Activated Protein Kinases