Intravital lipid droplet labeling and imaging reveals the phenotypes and functions of individual macrophages in vivo.
Intravital lipid droplet labeling and imaging reveals the phenotypes and functions of individual macrophages in vivo.
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活体脂滴标记和成像揭示体内单个巨噬细胞的表型和功能
DOI：
10.1016/j.jlr.2022.100207
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发表时间：
2022-05
影响因子：
6.5
通讯作者：
Zeng L
中科院分区：
文献类型：
--
作者：
Li Y;Du Y;Xu Z;He Y;Yao R;Jiang H;Ju W;Qiao J;Xu K;Liu TM;Zeng L
巨噬细胞在维持组织内稳态中起着关键作用。然而，巨噬细胞向促炎状态的再活化与过多的炎性疾病相关，包括动脉粥样硬化、肥胖、神经变性和骨髓（BM）衰竭综合征。缺乏方法来揭示体内巨噬细胞表型和功能阻碍了这些疾病的转化研究。在这里，我们发现促炎性巨噬细胞在体外和体内相对于静息或非炎性巨噬细胞积累细胞内脂滴（LD），表明LD积累作为巨噬细胞表型的结构生物标志物。为了实现体内巨噬细胞LDs的染色和成像，我们研制了一种高效、特异的荧光脂肪酸类似物聚乳酸-羟基乙酸纳米颗粒标记小鼠巨噬细胞。使用这些新的纳米颗粒，我们实现了在急性或慢性炎症条件下BM，肝，肺和脂肪组织中单个巨噬细胞的原位功能鉴定。此外，利用该活体成像平台，我们进一步实现了全身炎症下小鼠颅骨BM中单个巨噬细胞的体内表型。总之，我们建立了一个有效的体内LD标记和成像系统的单个巨噬细胞表型，这将有助于诊断和治疗监测的发展。此外，该方法也为研究体内脂质的运输和动力学提供了新的途径。
Macrophages play pivotal roles in the maintenance of tissue homeostasis. However, the reactivation of macrophages toward proinflammatory states correlates with a plethora of inflammatory diseases, including atherosclerosis, obesity, neurodegeneration, and bone marrow (BM) failure syndromes. The lack of methods to reveal macrophage phenotype and function in vivo impedes the translational research of these diseases. Here, we found that proinflammatory macrophages accumulate intracellular lipid droplets (LDs) relative to resting or noninflammatory macrophages both in vitro and in vivo, indicating that LD accumulation serves as a structural biomarker for macrophage phenotyping. To realize the staining and imaging of macrophage LDs in vivo, we developed a fluorescent fatty acid analog-loaded poly(lactic-co-glycolic acid) nanoparticle to label macrophages in mice with high efficiency and specificity. Using these novel nanoparticles, we achieved in situ functional identification of single macrophages in BM, liver, lung, and adipose tissues under conditions of acute or chronic inflammation. Moreover, with this intravital imaging platform, we further realized in vivo phenotyping of individual macrophages in the calvarial BM of mice under systemic inflammation. In conclusion, we established an efficient in vivo LD labeling and imaging system for single macrophage phenotyping, which will aid in the development of diagnostics and therapeutic monitoring. Moreover, this method also provides new avenues for the study of lipid trafficking and dynamics in vivo.
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影响因子：
5
作者：
Makadia HK;Siegel SJ
通讯作者：
Siegel SJ
人体胎盘中Bodipy-C12长链脂肪酸的实时跟踪揭示了细胞增生细胞细胞中独特的脂质动力学。
影响因子：
3.7
作者：
Kolahi K;Louey S;Varlamov O;Thornburg K
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影响因子：
7.7
作者：
Ghosh AC;Tattikota SG;Liu Y;Comjean A;Hu Y;Barrera V;Ho Sui SJ;Perrimon N
通讯作者：
Perrimon N
影响因子：
3.4
作者：
Akhoundi, Farhad;Qin, Yukun;Kieu, Khanh
通讯作者：
Kieu, Khanh
影响因子：
4.8
作者：
Huang, Ying-ling;Morales-Rosado, Joel;Munford, Robert S.
通讯作者：
Munford, Robert S.