Excessive infiltration of pro-inflammatory monocytes /macrophages early after myocardial ischemia/reperfusion (MI/R) contributes to myocardial injury and cardiac dysfunction. We tested the hypothesis that conditional depletion of pro-inflammatory macrophages and dendritic cells may dampen excessive inflammatory response in the infarct myocardium, and thus attenuate MI/R injury. To achieve this, we took advantage of CD11c-diphtheria toxin receptor (DTR) transgenic mice, which allow for selective and conditional ablation of CD11c
+
cells for 2-3 days after diphtheria toxin administration. CD11c-DTR mice with conditional deficiency of CD11c
+
cells and wild type (WT) mice were subjected to MI/R (30 min /48 h). CD11c-DTR mice showed decreased infiltration of CD11c
+
dendritic cells and CD11c
+
F4/80
+
macrophages in the I/R heart, reduced infarct size, attenuated myocardium apoptosis and improved cardiac function compared with those in WT mice. Moreover, inflammatory cytokines, such as TNF-α, MCP-1 and IFN-γ in the infracted myocardium as well as myocardial nitrotyrosine level, an index of oxidative and nitrative stresses, were dramatically decreased in CD11c-DTR mice than those in WT mice. These data indicate that the decreased infiltration of pro-inflammatory macrophages /dendritic cells and subsequent ameliorated inflammation may contribute to attenuated reperfusion injury and better reserved cardiac function in CD11c-DTR mice. This may provide potential novel strategies to target pro-inflammatory cells to reduce detrimental effects while sparing the beneficial wound healing roles of the recruited macrophages.
CD39 expression by hepatic myeloid dendritic cells attenuates inflammation in liver transplant ischemia-reperfusion injury in mice