Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
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DOI：
10.1172/jci200522675
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发表时间：
2005-01-01
影响因子：
15.9
通讯作者：
Iredale, JP
中科院分区：
文献类型：
--
作者：
Duffield, JS;Forbes, SJ;Iredale, JP
巨噬细胞在不同的炎症模型中执行损伤诱导和修复促进任务，导致巨噬细胞功能模型中不同的激活模式被提出。我们在一个损伤和恢复阶段不同的可逆肝损伤模型中研究了巨噬细胞的机制功能。四氯化碳诱导的肝纤维化显示，疤痕相关的巨噬细胞在整个恢复过程中持续存在。制备了巨噬细胞可选择性清除的转基因小鼠（CD11b-DTR）。肝纤维化进展时巨噬细胞耗竭导致瘢痕减少和肌成纤维细胞减少。相比之下，在恢复过程中巨噬细胞消耗导致基质降解失败。这些数据提供了第一个明确的证据，证明在同一组织中存在功能不同的巨噬细胞亚群，这些巨噬细胞在炎症瘢痕的损伤和恢复阶段都起着关键作用。
Macrophages perform both injury-inducing and repair-promoting tasks in different models of inflammation, leading to a model of macrophage function in which distinct patterns of activation have been proposed. We investigated macrophage function mechanistically in a reversible model of liver injury in which the injury and recovery phases are distinct. Carbon tetrachloride-induced liver fibrosis revealed scar-associated macrophages that persisted throughout recovery. A transgenic mouse (CD11b-DTR) was generated in which macrophages could be selectively depleted. Macrophage depletion when liver fibrosis was advanced resulted in reduced scarring and fewer myofibroblasts. Macrophage depletion during recovery, by contrast, led to a failure of matrix degradation. These data provide the first clear evidence that functionally distinct subpopulations of macrophages exist in the same tissue and that these macrophages play critical roles in both the injury and recovery phases of inflammatory scarring.