中文摘要:
炎癥的持續存在及其對組織再生的相關限制,被認為部分歸因于M1型巨噬細胞相對于M2型巨噬細胞的失衡。在此,我們假設提供一種持續釋放的抗炎性極化細胞因子,能夠改變組織損傷部位巨噬細胞的平衡,從而改善功能性再生。具體而言,我們將IL-4偶聯金納米顆粒(PA4)注射至小鼠受損骨骼肌中,結果顯示,與僅注射溶劑的對照組小鼠相比,PA4治療組小鼠的組織學表現得到改善,肌肉力量提高了約40%。巨噬細胞是主要的浸潤免疫細胞,與溶劑對照組相比,PA4治療組中表達M2a表型的巨噬細胞比例增加了約兩倍,而M1型巨噬細胞比例則減少了約兩倍。肌肉注射可溶性IL-4未能在功能上改善肌肉,也未改變巨噬細胞的極化狀態。荷蘭Liposoma氯膦酸鹽脂質體單核/巨噬細胞的耗竭消除了PA4的治療效果,表明肌肉功能的改善源于向M2型巨噬細胞極化的轉變。PA4在體內引導巨噬細胞極化的能力,可能對多種損傷和炎癥性疾病的治療具有潛在益處。
英文摘要:
Persistence of inflammation, and associated limits in tissue regeneration, are believed to be due in part to the imbalance of M1 over M2 macrophages. Here, we hypothesized that providing a sustained source of an antiinflammatory polarizing cytokine would shift the balance of macrophages at a site of tissue damage to improve functional regeneration. Specifically, IL-4–conjugated gold nanoparticles (PA4) were injected into injured murine skeletal muscle, resulting in improved histology and an ~40% increase in muscle force compared with mice treated with vehicle only. Macrophages were the predominant infiltrating immune cell, and treatment with PA4 resulted in an approximately twofold increase in the percentage of macrophages expressing the M2a phenotype and an approximately twofold decrease in M1 macrophages, compared with mice treated with vehicle only. Intramuscular injection of soluble IL-4 did not shift macrophage polarization or result in functional muscle improvements. Depletion of monocytes/macrophages eliminated the therapeutic effects of PA4, suggesting that improvement in muscle function was the result of M2-shifted macrophage polarization. The ability of PA4 to direct macrophage polarization in vivo may be beneficial in the treatment of many injuries and inflammatory diseases.
論文信息:
論文題目:Functional muscle recovery with nanoparticle-directed M2 macrophage polarization in mice
期刊名稱:PNAS
時間期卷:115 (42) 10648-10653
DOI: 10.1073/pnas.1806908115
產品信息:
貨號:CP-010-010
規格:10ml+10ml
品牌:Liposoma
產地:荷蘭
名稱:Clodronate Liposomes&Control Liposomes
辦事處:靶點科技
Clodronate Liposomes氯膦酸鹽脂質體清除肌肉巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于PNAS:通過納米顆粒引導M2型巨噬細胞極化實現小鼠功能性肌肉恢復。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法:
In vivo macrophage depletion
Macrophage Depletion. Clodronate and PBS liposomes were purchased from Liposoma (SKU: LIP-01). Liposomes (70uL) were administered retro-orbitally 2 days before surgery, and again on days 1 and 5 after surgery (Fig. S1A); 10uL were also administered intramuscularly into the ischemic TA 1 day before surgery, and again on days 2 and 7 after surgery.
巨噬細胞清除材料和方法文獻截圖:

