In vivo characterization of alveolar and interstitial lung macrophages in rhesus macaques: implications for understanding lung disease in humans.
In vivo characterization of alveolar and interstitial lung macrophages in rhesus macaques: implications for understanding lung disease in humans.
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DOI：
10.4049/jimmunol.1302269
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发表时间：
2014-03-15
期刊：
影响因子：
--
通讯作者：
Kuroda MJ
中科院分区：
文献类型：
--
作者：
Cai Y;Sugimoto C;Arainga M;Alvarez X;Didier ES;Kuroda MJ
通过支气管肺泡灌洗(BAL)获得的肺泡巨噬细胞(AM)常用于研究肺巨噬细胞介导的免疫反应。然而，AM是否完全代表肺中巨噬细胞的功能仍然存在疑问。这项研究是为了确定肺组织间质巨噬细胞(IM)对肺免疫的贡献，这些细胞在BAL样本中不存在。采用体内注射BrdU的方法，研究了恒河猴(Macaca Mulatta)体内单核/组织巨噬细胞的代谢动力学和单核/组织巨噬细胞的转化。用流式细胞仪和免疫组织化学方法分析肺巨噬细胞表型和细胞转化率。恒河猴肺内AM和IM约占肺内免疫反应细胞的70%。AM代表较大比例的巨噬细胞，大约75-80%，并且表现出最小的周转。相反，IM表现出更高的周转率，与稳态时单核细胞的周转率相似。IM的TdT介导的dUTP缺口末端标记(TUNEL)染色也较高，提示单核细胞取代IM发生了持续的细胞凋亡。尽管AM在稳态状态下表现为静止状态，但在BAL手术后观察到单核细胞/IM来源的新AM内流增加。此外，体外干扰素-γ联合脂多糖治疗可显著增加IM细胞内肿瘤坏死因子-α的表达，但对AM无明显影响这些发现表明，从BAL获得的较长寿命的AM可能不代表巨噬细胞反应的整个肺光谱，而较短寿命的IM可能作为肺内关键的粘膜巨噬细胞亚群发挥作用，帮助维持体内平衡并保护其免受环境中持续的病原体暴露。
Alveolar macrophages (AM) obtained by bronchoalveolar lavage (BAL) are commonly used to study lung macrophage-mediated immune responses. Questions remain, however, about whether AM fully represent macrophage function in the lung. This study was performed to determine the contribution of interstitial macrophages (IM) of lung tissue to pulmonary immunity and that are not present in BAL sampling. In vivo BrdU injection was performed to evaluate the kinetics and monocyte/tissue macrophage turnover in Indian rhesus macaques (Macaca mulatta). Lung macrophage phenotype and cell turnover were analyzed by flow cytometry and immunohistochemistry. AM and IM in lungs of rhesus macaques comprised about 70% of immune response cells in the lung. AM represented a larger proportion of macrophages, approximately 75–80%, and exhibited minimal turnover. Conversely, IM exhibited higher turnover rates that were similar to those of blood monocytes during steady state homeostasis. IM also exhibited higher staining for TdT-mediated dUTP nick end labeling (TUNEL), suggesting a continuous transition of blood monocytes replacing IM undergoing apoptosis. Although AM appear static in steady state homeostasis, increased influx of new AM derived from monocytes/IM was observed following BAL procedure. Moreover, ex vivo IFN-γ plus LPS treatment significantly increased intracellular expression of TNF-α in IM but not in AM. These findings indicate that the longer-lived AM obtained from BAL may not represent the entire pulmonary spectrum of macrophage responses, and shorter-lived IM may function as the critical mucosal macrophage subset in the lung that helps to maintain homeostasis and protect against continuous pathogen exposure from the environment.
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影响因子：
5.4
作者：
Gordon, Siamon;Hamann, Joerg;Stacey, Martin
通讯作者：
Stacey, Martin
影响因子：
5.4
作者：
Hamann, Jorg;Koning, Nathalie;Kwakkenbos, Mark J.
通讯作者：
Kwakkenbos, Mark J.
影响因子：
9.8
作者：
Church DM;Goodstadt L;Hillier LW;Zody MC;Goldstein S;She X;Bult CJ;Agarwala R;Cherry JL;DiCuccio M;Hlavina W;Kapustin Y;Meric P;Maglott D;Birtle Z;Marques AC;Graves T;Zhou S;Teague B;Potamousis K;Churas C;Place M;Herschleb J;Runnheim R;Forrest D;Amos-Landgraf J;Schwartz DC;Cheng Z;Lindblad-Toh K;Eichler EE;Ponting CP;Mouse Genome Sequencing Consortium
通讯作者：
Mouse Genome Sequencing Consortium
DOI：
10.1073/pnas.1222878110
发表时间：
2013-02-26
影响因子：
11.1
作者：
Seok, Junhee;Warren, H. Shaw;Tompkins, Ronald G.
通讯作者：
Tompkins, Ronald G.
影响因子：
2.2
作者：
Barletta, Kathryn E.;Cagnina, R. Elaine;Wallace, Kori L.;Ramos, Susan I.;Mehrad, Borna;Linden, Joel
通讯作者：
Linden, Joel