Regulatory Role of Dendritic Cells in Postinfarction Healing and Left Ventricular Remodeling

• DOI: 10.1161/circulationaha.111.052126
• Publication Date: 2012-02-04T04:45:19Z
• Authors: Atsushi Anzai; Toshihisa Anzai; Shigenori Nagai; Yuichiro Maekawa; Kotaro Naito; Hidehiro Kaneko; Yasuo Sugano; Toshiyuki Takahashi; Hitoshi Abe; Satsuki Mochizuki; Motoaki Sano; Tsutomu Yoshikawa; Yasunori Okada; Shigeo Koyasu; Satoshi Ogawa; Keiichi Fukuda
• Keywords: CD11c; Proinflammatory cytokine; Ventricular remodeling; Monocyte

Background— Inflammation and immune responses are integral components in the healing process after myocardial infarction. We previously reported dendritic cell (DC) infiltration infarcted heart; however, precise contribution of DC postinfarction is unclear. Methods Results— Bone marrow cells from CD11c-diphtheria toxin receptor/green fluorescent protein transgenic mice were transplanted into lethally irradiated wild-type recipient mice. After reconstitution bone marrow–derived cells, treated with either diphtheria (DC ablation) or vehicle (control), infarction was created by left coronary ligation. CD11c + green protein–positive DCs expressing CD11b major histocompatibility complex class II recruited heart, peaking on day 7 control group. Mice ablation for days showed deteriorated ventricular function remodeling. The DC-ablated group demonstrated enhanced sustained expression inflammatory cytokines such as interleukin-1β, interleukin-18, tumor necrosis factor-α, prolonged extracellular matrix degradation associated a high level metalloproteinase-9 activity, diminished interleukin-10 endothelial proliferation compared In vivo analyses revealed that infarcts had monocyte/macrophage recruitment. Among these marked proinflammatory Ly6C monocytes F4/80 CD206 − M1 macrophages and, conversely, impaired recruitment anti-inflammatory low M2 myocardium identified Conclusions— These results suggest potent immunoprotective regulator during via its homeostasis.