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Updated: Jun 26, 2026

Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
Published on: June 30, 2016
Activated monocytes induce smooth muscle cell death: role of macrophage colony-stimulating factor and cell contact
Puvi N Seshiah1, Dean J Kereiakes, Sanjay S Vasudevan
1Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, USA.
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< or =0.00005), VSMCs plus MMs without M-CSF (22.7+/-3.7%, P< or =0.0001), or control VSMCs alone (13.2+/-2.1%, P< or =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 microg/mL) significantly reduced VSMC apoptosis (19.1+/-2.2%, P< or =0.0003). Therapeutic doses of tirofiban (0.35 microg/mL) and eptifibatide (5 microg/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.
Insights
Monocytes and macrophage colony-stimulating factor (M-CSF) trigger vascular smooth muscle cell (VSMC) death. The drug abciximab, targeting the Mac-1 receptor, can prevent this process, offering potential therapeutic avenues for cardiovascular events.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cellular Pathology
Background:
- Plaque disruption is a key event in coronary thrombosis and acute coronary syndromes.
- Loss of vascular smooth muscle cells (VSMCs) contributes to plaque instability.
- Monocytes/macrophages (MMs) activated by macrophage colony-stimulating factor (M-CSF) are implicated in VSMC death.
Purpose of the Study:
- To investigate the role of M-CSF-activated MMs in VSMC apoptosis.
- To identify potential therapeutic targets for preventing M-CSF-induced VSMC death.
Main Methods:
- VSMC apoptosis was quantified in the presence of MMs and/or M-CSF.
- The effect of abciximab, tirofiban, eptifibatide, and an anti-CD-18 antibody on VSMC apoptosis was assessed.
- MM-VSMC interaction and M-CSF concentration dependency were evaluated.
Main Results:
- M-CSF-activated MMs significantly increased VSMC apoptosis compared to controls.
- MM cell contact was essential for M-CSF-stimulated VSMC killing.
- Abciximab, which binds Mac-1 on MMs, significantly reduced VSMC apoptosis.
- Tirofiban and eptifibatide, which do not inhibit Mac-1, did not prevent VSMC apoptosis.
Conclusions:
- Monocytes and M-CSF induce VSMC apoptosis.
- Inhibitors of the Mac-1 receptor, such as abciximab, can antagonize this apoptotic process.
- Targeting the Mac-1 pathway may offer a therapeutic strategy for acute coronary syndromes.
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