PDF(Pubmed)
Abstract：
Tissue-resident macrophages are of vital importance as they preserve tissue homeostasis in all mammalian organs. Nevertheless, appropriate cell culture models are still limited. Here, we propose a novel culture model to study and expand murine primary alveolar macrophages (AMs), the tissue-resident macrophages of the lung, in vitro over several months. By providing a combination of granulocyte-macrophage colony-stimulating factor, TGFβ, and the PPARγ activator rosiglitazone, we maintain and expand mouse ex vivo cultured AMs (mexAMs) over several months. MexAMs maintain typical morphologic features and stably express primary AM surface markers throughout in vitro culture. They respond to microbial ligands and exhibit an AM-like transcriptional profile, including the expression of AM-specific transcription factors. Furthermore, when transferred into AM-deficient mice, mexAMs efficiently engraft in the lung and fulfill key macrophage functions, leading to a significantly reduced surfactant load in those mice. Altogether, mexAMs provide a novel, simple, and versatile tool to study AM behavior in homeostasis and disease settings.
摘要：
组织驻留的巨噬细胞至关重要，因为它们可以保持所有哺乳动物器官的组织稳态。然而，适当的细胞培养模型仍然有限。这里,我们提出了一种新的培养模型来研究和扩展小鼠原代肺泡巨噬细胞（AMs），肺的组织驻留巨噬细胞，在体外几个月。通过提供粒细胞-巨噬细胞集落刺激因子的组合，TGFβ,和PPARγ激活剂罗格列酮，我们维持和扩大小鼠离体培养的AMs（mexAMs）几个月。MexAM在整个体外培养中保持典型的形态特征并稳定表达初级AM表面标记。它们响应微生物配体并表现出AM样转录谱，包括AM特异性转录因子的表达。此外，当转移到缺乏AM的小鼠中时，mexAMs有效地移植到肺中并实现关键的巨噬细胞功能，导致这些小鼠的表面活性剂负荷显著降低。总之,mexAMs提供了一部小说，简单,以及研究稳态和疾病环境中AM行为的多功能工具。
