Inhibition of endothelial cell proliferation by platelet factor-4 involves a unique action on S phase progression.
Inhibition of endothelial cell proliferation by platelet factor-4 involves a unique action on S phase progression.
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DOI：
10.1083/jcb.127.4.1121
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发表时间：
1994-11
期刊：
影响因子：
--
通讯作者：
Singh JP
中科院分区：
文献类型：
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作者：
Gupta SK;Singh JP
研究了“趋化因子”血小板因子-4（PF-4）对内皮细胞增殖和细胞周期进程的调节作用。PF-4抑制DNA合成，以及来自大小血管的内皮细胞的增殖。PF-4的抑制作用与用于诱导内皮细胞增殖的刺激物的类型和浓度无关。PF-4对细胞生长的抑制是可逆的。PF-4的作用可被肝素拮抗。用[3 H]胸苷脉冲标记法分析同步化细胞从G 0/G1期进入S期的细胞周期，发现在G1期加入PF-4可完全阻断细胞进入S期。此外，PF-4还抑制已处于S期的细胞的DNA合成。在指数生长的细胞中，加入PF-4导致> 70%的细胞在早期S期积累，如通过FACS（Becton-Dickinson Immunocytometry Systems，山景，CA）测定的。在S期同步的细胞中，通过羟基脲，然后释放，加入PF-4迅速阻断DNA合成的进一步进展。这些结果表明，在G 0/G1-停滞的细胞中，PF-4抑制内皮细胞进入S期。更引人注目的是，我们的研究揭示了一种独特的内皮细胞生长抑制模式，PF-4有效地阻断了S期细胞周期的进展。
Modulation of endothelial cell proliferation and cell cycle progression by the "chemokine" platelet factor-4 (PF-4) was investigated. PF-4 inhibited DNA synthesis, as well as proliferation of endothelial cells derived from large and small blood vessels. Inhibition by PF-4 was independent of the type and the concentration of stimuli used for the induction of endothelial cell proliferation. Inhibition of cell growth by PF-4 was reversible. The effects of PF-4 were antagonized by heparin. Cell cycle analysis using [3H]thymidine pulse labeling during traverse of synchronous cells from G0/G1 to S phase revealed that addition of PF-4 during G1 phase completely abolished the entry of cells into S phase. In addition, PF-4 also inhibited DNA synthesis in cells that were already in S phase. In exponentially growing cells, addition of PF-4 resulted in an accumulation of > 70% of the cells in early S phase, as determined by FACS (Becton-Dickinson Immunocytometry Systems, Mountain View, CA). In cells synchronized in S phase by hydroxyurea and then released, addition of PF-4 promptly blocked further progression of DNA synthesis. These results demonstrate that in G0/G1-arrested cells, PF-4 inhibited entry of endothelial cells into S phase. More strikingly, our studies have revealed a unique mode of endothelial cell growth inhibition whereby PF-4 effectively blocked cell cycle progression during S phase.