Abstract 12240: Dendritic Cell is an Immunoprotective Regulator 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 into the infarcted heart. This study was designed to elucidate whether and how DC contributes to post-infarction healing and left ventricular (LV) remodeling.
Methods and Results- Bone-marrow (BM) cells from CD11c-diphtheria toxin receptor (DTR)/green fluorescent protein (GFP) transgenic mice were transplanted into lethally irradiated wild-type (WT) recipient mice. After reconstitution of BM-derived cells, the recipient mice were treated with either diphtheria toxin (DC-ablation group) or vehicle (control group), 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 depletion for 7 days showed increased mortality, and deteriorated LV dysfunction and remodeling 28 days after MI. DC-ablation group demonstrated enhanced and sustained expression of proinflammatory cytokines such as interleukin (IL)-1β, IL-18 and tumor necrosis factor-α, prolonged extracellular matrix degradation associated with high levels of matrix metalloproteinase-9 activity, and increased cardiac apoptosis compared with control group. Augmented infiltration of inflammatory Ly6Chigh monocytes and macrophages into the infarcted heart was also observed in DC-ablation group. Expression levels of anti-inflammatory cytokine, IL-10, and the number of Ly6Clow monocytes in the infarcted myocardium on day 7 were significantly lower in DC-ablation group than in control group. Adoptive transfer of BM-derived DCs from WT, but not IL-10 deficient mice abrogated the adverse effects of DC depletion on post-infarction LV remodeling.
Conclusions- Selective DC depletion resulted in exacerbated LV remodeling after MI in association with enhanced inflammation, extracellular matrix degradation and cardiac apoptosis. DC is a potent immunoprotective regulator during the post-infarction healing process, especially in monocytes/macrophages homeostasis partly through IL-10 secretion, and modulation of DC could be a new therapeutic target in LV remodeling after MI.
- © 2011 by American Heart Association, Inc.