Inhibition of endothelial cell proliferation by platelet factor-4 involves a unique action on S phase progression

Shalley K. Gupta, Jai Pal Singh

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1121-1127
Number of pages7
JournalJournal of Cell Biology
Volume127
Issue number4
DOIs
StatePublished - Nov 1 1994

ASJC Scopus subject areas

  • Cell Biology

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