Remodeling of the mononuclear phagocyte network underlies chronic inflammation and disease progression in heart failure: critical importance of the cardiosplenic axis.
Remodeling of the mononuclear phagocyte network underlies chronic inflammation and disease progression in heart failure: critical importance of the cardiosplenic axis.
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DOI：
10.1161/circresaha.113.301720
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发表时间：
2014-01-17
影响因子：
20.1
通讯作者：
Prabhu SD
中科院分区：
文献类型：
--
作者：
Ismahil MA;Hamid T;Bansal SS;Patel B;Kingery JR;Prabhu SD
单核吞噬细胞在慢性心力衰竭（HF）中的作用尚不清楚。我们的目的是描述单核细胞、巨噬细胞和树突状细胞在HF中的运输，并确定脾脏对心脏重塑的贡献。我们评估了冠状动脉结扎后8周慢性HF的C57 B1/6小鼠。与假手术对照组相比，HF小鼠表现出：（1）心脏和外周血中的促炎性CD 11b +F4/80+ CD 206 −巨噬细胞和CD 11b +F4/80+Gr-1hi单核细胞分别增加，脾脏中的CD 11b +F4/80+Gr-1hi单核细胞减少;（2）心脏和脾脏中的CD 11 c +B220−经典树突状细胞和CD 11 c +/lowB 220+浆细胞样树突状细胞显著增加，外周血和骨髓中典型树突状细胞和浆细胞样树突状细胞分别增加：（3）脾脏中CD 4+辅助性T细胞和CD 8+细胞毒性T细胞增加;（4）脾组织结构发生明显改变，出现大量白色髓滤泡，边缘区和生发中心明显增大，Alarmins表达增加。脾切除术在建立HF小鼠逆转病理性心脏重塑和炎症。从HF小鼠过继转移的脾细胞，但不是从假手术小鼠，归巢到心脏，并诱导长期的左心室扩张，功能障碍和纤维化的幼稚受体。HF小鼠也表现出类似于HF小鼠的单核细胞活化和脾重塑。单核吞噬细胞的激活是HF心脏重塑进展的中心，脾中抗原处理的增强在此过程中起关键作用。脾细胞（可能是脾单核细胞和树突状细胞）在衰竭的心脏中促进免疫介导的损伤反应，并在过继转移时保留这种记忆。
The role of mononuclear phagocytes in chronic heart failure (HF) is unknown. Our aim was to delineate monocyte, macrophage, and dendritic cell trafficking in HF and define the contribution of the spleen to cardiac remodeling. We evaluated C57Bl/6 mice with chronic HF 8 weeks after coronary ligation. As compared with sham-operated controls, HF mice exhibited: (1) increased proinflammatory CD11b+F4/80+CD206− macrophages and CD11b+F4/80+Gr-1hi monocytes in the heart and peripheral blood, respectively, and reduced CD11b+F4/80+Gr-1hi monocytes in the spleen; (2) significantly increased CD11c+B220− classical dendritic cells and CD11c+/lowB220+ plasmacytoid dendritic cells in both the heart and spleen, and increased classic dendritic cells and plasmacytoid dendritic cells in peripheral blood and bone marrow, respectively; (3) increased CD4+ helper and CD8+ cytotoxic T-cells in the spleen; and (4) profound splenic remodeling with abundant white pulp follicles, markedly increased size of the marginal zone and germinal centers, and increased expression of alarmins. Splenectomy in mice with established HF reversed pathological cardiac remodeling and inflammation. Splenocytes adoptively transferred from mice with HF, but not from sham-operated mice, homed to the heart and induced long-term left ventricular dilatation, dysfunction, and fibrosis in naive recipients. Recipient mice also exhibited monocyte activation and splenic remodeling similar to HF mice. Activation of mononuclear phagocytes is central to the progression of cardiac remodeling in HF, and heightened antigen processing in the spleen plays a critical role in this process. Splenocytes (presumably splenic monocytes and dendritic cells) promote immune-mediated injurious responses in the failing heart and retain this memory on adoptive transfer.