The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.
The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.
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DOI：
10.1186/s40169-015-0047-4
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发表时间：
2015
影响因子：
10.6
通讯作者：
Jimenez SA
中科院分区：
文献类型：
--
作者：
Wermuth PJ;Jimenez SA
全身性和特定于器官的人类纤维性疾病共同构成了世界范围内最严重的健康问题之一，造成了世界人口总死亡率的很大比例。其发病机制是复杂的，尽管进行了深入的研究，但仍未完全阐明。尽管慢性炎症细胞在纤维化病变中普遍存在，但单核细胞和巨噬细胞作为炎症和纤维化调节细胞的中心作用直到最近才变得明显。然而，单核/巨噬细胞参与纤维化过程的启动、建立或进展的确切机制仍然很大程度上是未知的。一些单核细胞和巨噬细胞亚群已被确定，某些表型促进炎症，而其他表型则显示促纤维化作用。鉴于对纤维增生性疾病的有效治疗的需求尚未得到满足，以及单核/巨噬细胞亚群在纤维化形成中的关键调节作用，针对特定的单核/巨噬细胞亚群的治疗策略的开发已变得越来越有吸引力。我们将在这里概述目前对单核/巨噬细胞表型亚群在组织纤维化动物模型中的作用以及在各种全身和器官特异性人类纤维化疾病中的作用的理解。此外，我们将讨论通过针对不同单核细胞和巨噬细胞亚群之间的表型差异来设计有效的抗纤维化治疗干预措施的最新方法。
The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations.