Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.
Blood. 2012 Feb 23;119(8):1810-20. doi: 10.1182/blood-2011-09-379214. Epub 2011 Dec 20.
Macrophage-colony stimulating factor (CSF-1) signaling through its receptor (CSF-1R) promotes the differentiation of myeloid progenitors into heterogeneous populations of monocytes, macrophages, dendritic cells, and bone-resorbing osteoclasts. In the periphery, CSF-1 regulates the migration, proliferation, function, and survival of macrophages, which function at multiple levels within the innate and adaptive immune systems. Macrophage populations elicited by CSF-1 are associated with, and exacerbate, a broad spectrum of pathologies, including cancer, inflammation, and bone disease. Conversely, macrophages can also contribute to immunosuppression, disease resolution, and tissue repair. Recombinant CSF-1, antibodies against the ligand and the receptor, and specific inhibitors of CSF-1R kinase activity have been each been tested in a range of animal models and in some cases, in patients. This review examines the potential clinical uses of modulators of the CSF-1/CSF-1R system. We conclude that CSF-1 promotes a resident-type macrophage phenotype. As a treatment, CSF-1 has therapeutic potential in tissue repair. Conversely, inhibition of CSF-1R is unlikely to be effective in inflammatory disease but may have utility in cancer.
巨噬细胞集落刺激因子（CSF-1）通过其受体（CSF-1R）信号转导促进髓系祖细胞分化为异质性的单核细胞、巨噬细胞、树突状细胞和破骨细胞。在外周组织中，CSF-1 调节巨噬细胞的迁移、增殖、功能和存活，这些细胞在固有和适应性免疫系统的多个层面发挥作用。CSF-1 诱导的巨噬细胞群体与广泛的病理状态有关，并使其恶化，包括癌症、炎症和骨骼疾病。相反，巨噬细胞也可以促进免疫抑制、疾病缓解和组织修复。重组 CSF-1、针对配体和受体的抗体以及 CSF-1R 激酶活性的特异性抑制剂已在一系列动物模型中进行了测试，并在某些情况下在患者中进行了测试。这篇综述探讨了 CSF-1/CSF-1R 系统调节剂的潜在临床用途。我们得出结论，CSF-1 促进了常驻型巨噬细胞表型。作为一种治疗方法，CSF-1 在组织修复方面具有治疗潜力。相反，抑制 CSF-1R 在炎症性疾病中可能无效，但在癌症中可能具有应用价值。
