Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, United States.
Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, United States.
Immunobiology. 2020 May;225(3):151952. doi: 10.1016/j.imbio.2020.151952. Epub 2020 May 5.
Macrophages fuse into multinucleated giant cells (MGC) in many pathological conditions. Despite MGC correlations with granulomas, their functional contribution to inflammation is relatively unknown. An in vitro mouse model of IL-4-induced bone marrow-derived macrophage fusion and microfiltration were used to generate enriched MGC and macrophage populations. Phenotypes were compared in response to well-known inflammatory stimuli, including lipopolysaccharide and crocidolite asbestos. Surface markers were assessed by flow cytometry: CD11b, CD11c, F4/80, and MHC II. Secreted cytokines were assessed by multiplex immunoassay: IFN-γ, IL-1β, IL-6, TNF-α, IL-10, IL-13, and IL-33. Results show that MGC maintained macrophage surface protein expression but lost the ability to produce a cytokine response. This suggests a potentially beneficial role of MGC in isolating the host from a foreign body without contributing to excessive inflammation. This study and future research using other stimulants and environments are important to gaining a fundamental MGC cell biology understanding. This will inform approaches to controlling the foreign body response to particle exposure, medical implants, and many diseases associated with granulomas.
巨噬细胞在许多病理条件下融合为多核巨细胞 (MGC)。尽管 MGC 与肉芽肿有关，但它们对炎症的功能贡献尚不清楚。使用体外 IL-4 诱导的骨髓来源的巨噬细胞融合和微滤来生成富含 MGC 和巨噬细胞的群体。通过比较对已知炎症刺激物（包括脂多糖和青石棉）的反应来比较表型。通过流式细胞术评估表面标记物：CD11b、CD11c、F4/80 和 MHC II。通过多重免疫分析评估分泌的细胞因子：IFN-γ、IL-1β、IL-6、TNF-α、IL-10、IL-13 和 IL-33。结果表明，MGC 保持巨噬细胞表面蛋白表达，但失去产生细胞因子反应的能力。这表明 MGC 在将宿主与异物隔离而不导致过度炎症方面具有潜在的有益作用。这项研究和未来使用其他刺激物和环境的研究对于深入了解 MGC 细胞生物学非常重要。这将为控制颗粒暴露、医疗植入物和许多与肉芽肿相关的疾病的异物反应提供信息。
