Abstract 8815: Role of Regulatory T Cells in Atheroprotective Effects of Granulocyte Colony-Stimulating Factor
Background We and others have previously reported that granulocyte colony-stimulating factor (G-CSF) prevents left ventricular remodeling and dysfunction after myocardial infarction in animal models and human. We have also reported that G-CSF inhibits the progression of atherosclerosis in animal models, but its precise mechanism is still elusive. Because G-CSF was recently reported to enhance the cell number and function of regulatory T cells (Tregs), we investigated whether Tregs are critical for the protective effects of G-CSF on atherosclerosis.
Methods We examined the effects of G-CSF (200 rg/kg) or saline on the atherosclerosis using apolipoprotein E-deficient (ApoE-/-) mice. Twelve-week-old male ApoE-/- mice were subcutaneously administrated with 200 μg/kg of G-CSF or same volume of saline once a day for 5 consecutive days per a week for 4 weeks. After 28 days of G-CSF or saline treatment, mice were sacrificed and analyzed the atherosclerotic area of the aortic root. To deplete the function of Tregs, we injected intraperitoneally anti-mouse CD25 antibody (PC61). Furthermore, to determine the effect of Tregs, we examined the effects of G-CSF on atherosclerosis using ApoE-/-/CD28-/- double knockout mice that lack Tregs.
Results Atherosclerotic lesion of aortic sinus was significantly reduced in the G-CSF-treated mice compared with the saline-treated mice (35% reduction, Pμ0.05). G-CSF reduced the expression level of interferon-γ by 31% and increased the expression level of interleukin-10 by 20% in atherosclerotic lesions of aortic sinus. G-CSF increased the number of CD4+CD25+ Tregs in lymph nodes and spleen, and enhanced the suppressive function of Tregs in vitro. G-CSF markedly increased the number of Foxp3-positive Tregs in atherosclerotic lesions of aortic sinus. Blood lipid concentrations were not significantly different between the G-CSF-treated mice and the saline-treated mice. Administration of anti-CD25 antibody (PC61) that depletes Tregs abrogated these atheroprotective effects of G-CSF. Moreover, in ApoE-/-/CD28-/- mice, the protective effects of G-CSF on atherosclerosis were not recognized.
Conclusions These findings suggest that Tregs play an important role in the atheroprotective effects of G-CSF.
- © 2011 by American Heart Association, Inc.