Mac-1 and Fas activities are concurrently required for execution of smooth muscle cell death by M-CSF-stimulated macrophages

Sanjay S. Vasudevan, Neuza H.M. Lopes, Puvi N. Seshiah, Tao Wang, Clay B. Marsh, Dean J. Kereiakes, Chunming Dong, Pascal J. Goldschmidt-Clermont

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Objective: We have previously shown that macrophage colony stimulating factor (M-CSF), a potent survival and mitogenic factor for monocytes/ macrophages (MM), enables MM to induce vascular smooth muscle cell (VSMC) apoptosis. The killing requires the binding of MM to VSMC via Mac-1 (CD11b/CD18) on MM and intracellular adhesion molecule-1 (ICAM-1) on VSMC. We hypothesized that, in addition to Mac-1 binding, the killing process requires the activation of the Fas-death receptor pathway, which can be blocked at the level of Fas-Fas ligand interaction. Methods and Results: Human peripheral blood monocytes and VSMC were isolated and cultured as previously described. Soluble Fas (sFas) was overexpressed in VSMC by transduction using adenovirus specifying soluble Fas (Ad3hsFas). M-CSF markedly increased the expression of ICAM-1 in VSMC, resulting in enhanced clustering of MM on the surface of VSMC (≥3 MM per VSMC). MM, but not VSMC, expressed Fas-ligand (FasL), and VSMC apoptosis was inhibited by secretion of sFas by VSMC upon Ad3sFas transduction. Conclusions: MM and M-CSF-induced VSMC killing requires MM binding to VSMC mediated by Mac-1 and ICAM-1, and Fas-FasL interaction.

Original languageEnglish (US)
Pages (from-to)723-733
Number of pages11
JournalCardiovascular Research
Volume59
Issue number3
DOIs
StatePublished - Sep 1 2003

Keywords

  • Apoptosis
  • Growth factors
  • Infection/inflammation
  • Macrophages
  • Smooth muscle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Mac-1 and Fas activities are concurrently required for execution of smooth muscle cell death by M-CSF-stimulated macrophages'. Together they form a unique fingerprint.

  • Cite this

    Vasudevan, S. S., Lopes, N. H. M., Seshiah, P. N., Wang, T., Marsh, C. B., Kereiakes, D. J., Dong, C., & Goldschmidt-Clermont, P. J. (2003). Mac-1 and Fas activities are concurrently required for execution of smooth muscle cell death by M-CSF-stimulated macrophages. Cardiovascular Research, 59(3), 723-733. https://doi.org/10.1016/S0008-6363(03)00514-5