Fleetwood Andrew J, Cook Andrew D, Hamilton John A
Arthritis and Inflammation Research Centre, Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville 3010, Victoria, Australia.
Crit Rev Immunol. 2005;25(5):405-28. doi: 10.1615/critrevimmunol.v25.i5.50.
GM-CSF was originally defined by its ability to generate in vitro granulocyte and macrophage colonies from bone marrow precursor cells. Apart from its physiological role in the control of alveolar macrophage development, it now appears more likely that its major role lies in its ability to govern the properties of the more mature myeloid cells of the granulocyte and macrophage lineages, particularly during host defence and inflammatory reactions. Recent evidence is summarized below for a key role for GM-CSF in inflammatory and autoimmune diseases, making it therefore worthy of consideration for targeting. Such evidence includes disease exacerbation following its administration and amelioration of disease in animal models by GM-CSF gene targeting or by anti-GM-CSF antibody blockade. This review summarizes the evidence supporting a major role for GM-CSF in inflammation and autoimmunity and its functions as major regulator governing granulocyte and macrophage lineage populations at all stages of maturation.
GM-CSF最初是根据其在体外从骨髓前体细胞生成粒细胞和巨噬细胞集落的能力来定义的。除了在控制肺泡巨噬细胞发育中的生理作用外,现在看来更有可能的是,其主要作用在于它能够控制粒细胞和巨噬细胞谱系中更成熟的髓样细胞的特性,特别是在宿主防御和炎症反应期间。以下总结了最近的证据,表明GM-CSF在炎症和自身免疫性疾病中起关键作用,因此值得考虑将其作为靶点。此类证据包括给予GM-CSF后疾病加重,以及通过GM-CSF基因靶向或抗GM-CSF抗体阻断在动物模型中改善疾病。本综述总结了支持GM-CSF在炎症和自身免疫中起主要作用的证据,以及其作为在成熟的各个阶段控制粒细胞和巨噬细胞谱系群体的主要调节因子的功能。