Neutrophil-activating activity and platelet-activating factor synthesis in cytokine-stimulated endothelial cells: Reduced activity in growth-arrested cells

Autor: Haruo Shintaku, Kazuo Kobayashi, Yoshiki Nishizawa, Tatsuji Takahashi, Nagatoshi Fujiwara, Masaaki Inaba, Nobuji Maeda, Seiichi Kitagawa, Fumihiko Hato
Rok vydání: 2007
Předmět:
Zdroj: Microvascular Research. 73:29-34
ISSN: 0026-2862
DOI: 10.1016/j.mvr.2006.08.002
Popis: 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.
Databáze: OpenAIRE