Neutrophil-activating activity and platelet-activating factor synthesis in cytokine-stimulated endothelial cells: reduced activity in growth-arrested cells.
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.
Takahashi
Tatsuji
T
Department of Physiology, Osaka City University Graduate School of Medicine, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. ttatsuji@med.osaka-cu.ac.jp
Nishizawa
Yoshiki
Y
Hato
Fumihiko
F
Shintaku
Haruo
H
Maeda
Nobuji
N
Fujiwara
Nagatoshi
N
Inaba
Masaaki
M
Kobayashi
Kazuo
K
Kitagawa
Seiichi
S
D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D049109:Cell Proliferation; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000906:Antibodies; D017077:Culture Media, Conditioned; D016207:Cytokines; D053583:Interleukin-1beta; D010879:Piperazines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D053778:Thiazolidines; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; C068679:YM 264; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases