Activated monocytes induce smooth muscle cell death role of macrophage colony-stimulating factor and cell contact

Puvi N. Seshiah, Dean J. Kereiakes, Sanjay S. Vasudevan, Neuza Lopes, Baogen Y. Su, Nicholas A. Flavahan, Pascal J. Goldschmidt-Clermont

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Background - Plaque disruption is the inciting event for coronary thrombosis and acute coronary syndromes. Multiple factors influence plaque rupture, including the loss of vascular smooth muscle cells (VSMCs). We hypothesized that monocytes/macrophages (MMs) activated by macrophage colony-stimulating factor (M-CSF) are responsible for VSMC death. Methods and Results - VSMC apoptosis was markedly increased in the presence of both M-CSF and MMs (58.8±3.3%) compared with VSMCs plus M-CSF without MMs (15.7±1.5%, P≤0.00005), VSMCs plus MMs without M-CSF (22.7±3.7%, P≤0.0001), or control VSMCs alone (13.2±2.1%, P≤0.0001). MM cell contact was required for M-CSF-stimulated killing of VSMCs, and MMs displayed an M-CSF concentration-dependent killing effect. Abciximab binds Mac-1 (CD11b/CD18) on MMs. When added to VSMCs exposed to MMs and M-CSF, abciximab (7 μg/mL) significantly reduced VSMC apoptosis (19.1±2.2%, P≤0.0003). Therapeutic doses of tirofiban (0.35 μg/mL) and eptifibatide (5 μg/mL), which inhibit platelet glycoprotein (GP) IIb/IIIa but not Mac-1, did not block activated MM-induced VSMC apoptosis (65.0±3.4% and 51.3±2.5%, respectively). A recombinant anti-CD-18 antibody had an effect similar to that of abciximab (16.5±0.4%). Conclusions - These data suggest that monocytes and physiological concentrations of M-CSF trigger VSMC apoptosis. Abciximab and specific inhibitors of the Mac-1 receptor can antagonize this process.

Original languageEnglish (US)
Pages (from-to)174-180
Number of pages7
JournalCirculation
Volume105
Issue number2
DOIs
StatePublished - Jan 15 2002

Keywords

  • Apoptosis
  • Cell adhesion molecules
  • Inflammation
  • Muscle, smooth
  • Plaque

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Seshiah, P. N., Kereiakes, D. J., Vasudevan, S. S., Lopes, N., Su, B. Y., Flavahan, N. A., & Goldschmidt-Clermont, P. J. (2002). Activated monocytes induce smooth muscle cell death role of macrophage colony-stimulating factor and cell contact. Circulation, 105(2), 174-180. https://doi.org/10.1161/hc0202.102248