Abstract 11405: Apob-100 Peptide-Primed Dendritic Cells Confers Athero-Protective Effect in Hypercholesterolemic Apoe-/- Mice
Background: Dendritic cells (DCs) play a pivotal role in atherogenesis and have been implicated in cholesterol homeostasis in hypercholesterolemic mice. LDL priming increases maturation of DCs, yet priming with apoB-100 and IL-10 induces tolerogenic DCs and their adoptive transfer reduced atherosclerosis. In this study, we hypothesized that priming DCs with an apoB-100 related peptide, p210, will modulate DC function and reduce atherosclerosis.
Methods and Results: Bone marrow cells from apoE-/- mice were used to obtain enriched DC cultures (BMDCs). In vitro priming of BMDCs with 100 ug/ml p210 for 20 hours did not alter cell phenotype but co-priming with LPS (100ng/ml) stimulation significantly reduced soluble IL-12 compared to LPS stimulation alone (96±62 vs 457±349 pg/ml, respectively; N=6 each; P<0.05), indicating modulation of maturing DCs by p210. No effect was observed in soluble IL-10. BMDCs primed with p210 for 20 hours were then adoptively transferred into normal chow-fed apoE-/- mice at 7 weeks of age at a dose of 2 × 106 cells per mouse via the tail vein. The cell transfer injections were repeated at 9 and 12 weeks of age; thereafter mice were switched to high cholesterol diet until euthanasia at 25 weeks of age. Unprimed BMDCs served as control. p210-primed BMDC transfer significantly reduced aortic sinus atherosclerotic plaque size, macrophage and lipid content, and lowered circulating cholesterol levels (Table).
Conclusion: Our results show that p210 priming renders DC less responsive to inflammatory stimulation and adoptive transfer of p210-primed DCs confers athero-protective effects. Reduced cholesterol levels in p210-primed DC recipient mice supports the notion that DCs are implicated in cholesterol homeostasis.
- © 2011 by American Heart Association, Inc.