Louis Cynthia, Cook Andrew D, Lacey Derek, Fleetwood Andrew J, Vlahos Ross, Anderson Gary P, Hamilton John A
Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia;
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3052, Australia;
J Immunol. 2015 Jul 1;195(1):134-44. doi: 10.4049/jimmunol.1500369. Epub 2015 May 27.
M-CSF (or CSF-1) and GM-CSF can regulate the development and function of the mononuclear phagocyte system (MPS). To address some of the outstanding and sometimes conflicting issues surrounding this biology, we undertook a comparative analysis of the effects of neutralizing mAbs to these CSFs on murine MPS populations in the steady-state and during acute inflammatory reactions. CSF-1 neutralization, but not of GM-CSF, in normal mice rapidly reduced the numbers of more mature Ly6C(-) monocytes in blood and bone marrow, without any effect on proliferating precursors, and also the numbers of the resident peritoneal macrophages, observations consistent with CSF-1 signaling being essential only at a relatively late state in steady-state MPS development; in contrast, GM-CSF neutralization had no effect on the numbers of these particular populations. In Ag-induced peritonitis (AIP), thioglycolate-induced peritonitis, and LPS-induced lung inflammation, CSF-1 neutralization lowered inflammatory macrophage number; in the AIP model, this reduced number was not due to suppressed proliferation. More detailed studies with the convenient AIP model indicated that CSF-1 neutralization led to a relatively uniform reduction in all inflammatory cell populations; GM-CSF neutralization, in contrast, was more selective, resulting in the preferential loss among the MPS populations of a cycling, monocyte-derived inflammatory dendritic cell population. Some mechanistic options for the specific CSF-dependent biologies enumerated are discussed.
巨噬细胞集落刺激因子（M-CSF，或CSF-1）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）可调节单核吞噬细胞系统（MPS）的发育和功能。为了解决围绕这一生物学特性的一些突出且有时相互矛盾的问题，我们对针对这些集落刺激因子的中和单克隆抗体对稳态和急性炎症反应期间小鼠MPS群体的影响进行了比较分析。在正常小鼠中，中和CSF-1而非GM-CSF可迅速减少血液和骨髓中更成熟的Ly6C(-)单核细胞数量，对增殖前体细胞无任何影响，同时也减少了驻留腹膜巨噬细胞的数量，这些观察结果表明CSF-1信号传导仅在稳态MPS发育的相对晚期才是必需的；相比之下，中和GM-CSF对这些特定群体的数量没有影响。在抗原诱导的腹膜炎（AIP）、巯基乙酸盐诱导的腹膜炎和脂多糖诱导的肺部炎症中，中和CSF-1可降低炎症巨噬细胞数量；在AIP模型中，数量减少并非由于增殖受到抑制。利用方便的AIP模型进行的更详细研究表明，中和CSF-1会导致所有炎症细胞群体相对均匀地减少；相比之下，中和GM-CSF更具选择性，导致循环的、单核细胞衍生的炎症树突状细胞群体在MPS群体中优先减少。文中讨论了所列举的特定集落刺激因子依赖性生物学特性的一些机制选择。
