The Elusive Antifibrotic Macrophage.
The Elusive Antifibrotic Macrophage.
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DOI：
10.3389/fmed.2015.00081
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发表时间：
2015
影响因子：
3.9
通讯作者：
Melgert BN
中科院分区：
文献类型：
--
作者：
Adhyatmika A;Putri KS;Beljaars L;Melgert BN
纤维化疾病，特别是肝脏、心血管系统、肾脏和肺部的纤维化疾病，占西方社会死亡人数的约45%。纤维化是一种与衰老和/或慢性炎症或损伤相关的严重并发症，目前尚不能有效治疗。其特征在于肌成纤维细胞的细胞外基质（ECM）蛋白过度沉积和巨噬细胞的降解受损。这最终会破坏器官的正常结构，导致功能丧失。大多数开发药物的努力都集中在抑制肌成纤维细胞产生ECM上，尚未产生许多有效的药物。另一种选择是刺激负责降解和摄取过量ECM的细胞，即，抗纤维化巨噬细胞然而，巨噬细胞是可塑细胞，在纤维化中有许多面孔，包括促纤维化行为刺激的ECM产生。这可能取决于它们的来源，因为不同的器官具有不同来源的组织驻留巨噬细胞，以及稳态条件下和纤维化期间进入的单核细胞的各种流入。为了能够在纤维化中刺激正确的行为，对抗纤维化巨噬细胞的彻底表征是必要的，以及了解它们降解ECM所需的信号。在这篇综述中，我们将总结目前的最先进的抗纤维化巨噬细胞表型和刺激其行为的信号。
Fibrotic diseases, especially of the liver, the cardiovascular system, the kidneys, and the lungs, account for approximately 45% of deaths in Western societies. Fibrosis is a serious complication associated with aging and/or chronic inflammation or injury and cannot be treated effectively yet. It is characterized by excessive deposition of extracellular matrix (ECM) proteins by myofibroblasts and impaired degradation by macrophages. This ultimately destroys the normal structure of an organ, which leads to loss of function. Most efforts to develop drugs have focused on inhibiting ECM production by myofibroblasts and have not yielded many effective drugs yet. Another option is to stimulate the cells that are responsible for degradation and uptake of excess ECM, i.e., antifibrotic macrophages. However, macrophages are plastic cells that have many faces in fibrosis, including profibrotic behavior-stimulating ECM production. This can be dependent on their origin, as the different organs have tissue-resident macrophages with different origins and a various influx of incoming monocytes in steady-state conditions and during fibrosis. To be able to pharmacologically stimulate the right kind of behavior in fibrosis, a thorough characterization of antifibrotic macrophages is necessary, as well as an understanding of the signals they need to degrade ECM. In this review, we will summarize the current state of the art regarding the antifibrotic macrophage phenotype and the signals that stimulate its behavior.