Regulatory Role of Dendritic Cells in Post-Infarction Healing and Left Ventricular Remodeling
Background—Inflammation and immune responses are integral components in the healing process after myocardial infarction (MI). We previously reported dendritic cell (DC) infiltration in the infarcted heart. However, the precise contribution of DC in post-infarction healing is unclear.
Methods and Results—Bone-marrow (BM) cells from CD11c-diphtheria toxin receptor/GFP transgenic mice were transplanted into lethally irradiated wild-type recipient mice. After reconstitution of BM-derived cells, the recipient mice were treated with either diphtheria toxin (DC-ablation) or vehicle (control), and MI was created by left coronary ligation. CD11c+ GFP+ DCs expressing CD11b and MHC class II were recruited into the heart, peaking on day 7 after MI in control group. Mice with DC-ablation for 7 days showed deteriorated left ventricular function and remodeling. DC-ablated group demonstrated enhanced and sustained expression of inflammatory cytokines such as interleukin (IL)-β, IL-18 and tumor necrosis factor-α, prolonged extracellular matrix degradation associated with a high level of matrix metalloproteinase-9 activity, and diminished expression level of IL-10 and endothelial cell proliferation following MI compared with control group. In vivo analyses revealed that DC-ablated infarcts had enhanced monocyte/macrophage recruitment. Among these cells, marked infiltration of proinflammatory Ly6Chigh monocytes and F4/80+ CD206- M1 macrophages, and conversely impaired recruitment of anti-inflammatory Ly6Clow monocytes and F4/80+ CD206+ M2 macrophages in the infarcted myocardium were identified in DC-ablated group than in control group.
Conclusions—These our results suggest that dendritic cell is a potent immunoprotective regulator during the post-infarction healing process, via controlling monocyte/macrophage homeostasis.
- Received July 9, 2011.
- Accepted January 9, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited