Characteristics of alveolar macrophages from murine models of OVA-induced allergic airway inflammation and LPS-induced acute airway inflammation

ABSTRACT<i>Background</i>: Macrophages include the classically activated pro-inflammatory M1 macrophages (M1s) and alternatively activated anti-inflammatory M2 macrophages (M2s). The M1s are activated by both interferon-γ and Toll-like receptor ligands, including lipopolysaccharide (LPS), and have potent pro-inflammatory activity. In contrast, Th2 cytokines activate the M2s, which are involved in the immune response to parasites, promotion of tissue remodeling, and immune regulatory functions. Although alveolar macrophages (AMs) play an essential role in the pulmonary immune system, little is known about their phenotypes. <i>Methods</i>: Quantitative reverse transcription polymerase chain reaction and flow cytometry were used to define the characteristics of alveolar macrophages derived from untreated naïve mice and from murine models of both ovalbumin (OVA)-induced allergic airway inflammation and LPS-induced acute airway inflammation. AMs were co-cultured with CD4⁺ T cells and were pulsed with tritiated thymidine to assess proliferative responses. <i>Results</i>: We characterized in detail murine AMs and found that these cells were not completely consistent with the current M1 versus M2-polarization model. OVA-induced allergic and LPS-induced acute airway inflammation promoted the polarization of AMs towards the current M2-skewed and M1-skewed phenotypes, respectively. Moreover, our data also show that CD11c⁺ CD11b⁺ AMs from the LPS-treated mice play a regulatory role in antigen-specific T-cell proliferation in vitro. <i>Conclusions</i>: These characteristics of AMs depend on the incoming pathogens they encounter and on the phase of inflammation and do not correspond to the current M1 versus M2-polarization model. These findings may facilitate an understanding of their contributions to the pulmonary immune system in airway inflammation.

摘要
<i>背景</i>：巨噬细胞（macrophages）可分为经典活化促炎性M1巨噬细胞（M1 macrophages, M1s）与替代活化抗炎性M2巨噬细胞（M2 macrophages, M2s）。M1巨噬细胞可经干扰素-γ与包括脂多糖（lipopolysaccharide, LPS）在内的Toll样受体配体活化，具备较强的促炎性活性。与之相对，Th2细胞因子可活化M2巨噬细胞，该类细胞参与寄生虫免疫应答、组织重塑调控及免疫调节功能。尽管肺泡巨噬细胞（alveolar macrophages, AMs）在肺部免疫系统中发挥不可或缺的作用，但目前对其表型特征的认知仍较为匮乏。
<i>方法</i>：本研究采用定量反转录聚合酶链反应与流式细胞术，对未致敏野生型小鼠、卵清蛋白（ovalbumin, OVA）诱导的变应性气道炎症模型小鼠以及脂多糖诱导的急性气道炎症模型小鼠来源的肺泡巨噬细胞进行系统表征。将肺泡巨噬细胞与CD4阳性T细胞共培养，并以氚标记胸腺嘧啶核苷进行脉冲标记，以评估细胞增殖反应。
<i>结果</i>：本研究对小鼠肺泡巨噬细胞进行了详细的表型分析，发现其并不完全契合当前的M1/M2极化模型。卵清蛋白诱导的变应性气道炎症与脂多糖诱导的急性气道炎症，可分别促使肺泡巨噬细胞向现有M2偏极化与M1偏极化表型转化。此外，本研究数据还证实，经脂多糖处理的小鼠来源的CD11c阳性CD11b阳性肺泡巨噬细胞，在体外可对抗原特异性T细胞增殖发挥调节作用。
<i>结论</i>：肺泡巨噬细胞的上述特征取决于其所接触的病原体类型以及炎症阶段，并不符合当前的M1/M2极化模型。本研究结果可为深入理解肺泡巨噬细胞在气道炎症中对肺部免疫系统的调控贡献提供理论依据。