中文摘要:
我們通過定位克隆技術確定了Ym1基因(存在一個重復序列和一個啟動子多態性)是炎癥的一個主要調控因子。具有RIIIS/J單倍型(該單倍型不表達Ym1)的小鼠,對甘露聚糖增強的膠原抗體誘導性關節炎,以及由鼻內暴露于甘露聚糖誘導的慢性關節炎,均表現出較低的易感性。 荷蘭Liposoma清除劑清除肺部巨噬細胞可緩解關節炎,而向Ym1缺陷小鼠鼻內補充Ym1蛋白則逆轉了疾病進程,這表明肺部巨噬細胞的Ym1在炎癥活性中起關鍵作用。
Ym1缺陷小鼠在患上肺炎后,表現為嗜酸性粒細胞浸潤減少,II型細胞因子和IgG1產生降低,并且由于STAT6激活增強,巨噬細胞向替代性激活方向偏移。蛋白質組學分析將Ym1多態性與脂質代謝的改變聯系起來。Ym1缺陷巨噬細胞中被誘導的PPAR-γ和脂質代謝變化促進了細胞的極化。
總之,Ym1的自然多態性通過調控與肺部炎癥相關的巨噬細胞替代性激活來發揮作用。
英文摘要:
We have positionally cloned the Ym1 gene, with a duplication and a promoter polymorphism, as a major regulator of inflammation. Mice with the RIIIS/J haplotype, with the absence of Ym1 expression, showed reduced susceptibility to mannan-enhanced collagen antibody–induced arthritis and to chronic arthritis induced by intranasal exposure of mannan. Depletion of lung macrophages alleviated arthritis, whereas intranasal supplement of Ym1 protein to Ym1-deficient mice reversed the disease, suggesting a key role of Ym1 for inflammatory activity by lung macrophages. Ym1-deficient mice with pneumonitis had less eosinophil infiltration, reduced production of type II cytokines and IgG1, and skewing of macrophages toward alternative activation due to enhanced STAT6 activation. Proteomics analysis connected Ym1 polymorphism with changed lipid metabolism. Induced PPAR-γ and lipid metabolism in Ym1-deficient macrophages contributed to cellular polarization. In conclusion, the natural polymorphism of Ym1 regulates alternative activation of macrophages associated with pulmonary inflammation.
論文信息:
論文題目:Natural polymorphism of Ym1 regulates pneumonitis through alternative activation of macrophages
期刊名稱:Science Advances
時間期卷:Vol 6, Issue43(2020)
在線時間:2020年10月21日
DOI: 10.1126/sciadv.aba9337
產品信息:
貨號:CP-005-005
規格:5ml+5ml
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肺炎模型小鼠體內肺泡巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Science Advances:Ym1的自然多態性通過巨噬細胞的替代性激活來調節肺炎。

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
Mice with Ncf1 mutation were administrated intranasally with 20 mg of mannan to induce psoriasis and PsA (24) and were scored daily for arthritis severity using the same scoring system as mentioned above. The severity of the psoriasis-like skin manifestations was monitored on a 15-score system, in which ears or each paw was evaluated by a scale ranging from 1 to 3 (1, weak skin peeling; 2, moderate skin peeling; and 3, heavy skin peeling with some hair loss) (24). For the in vivo macrophage depletion experiment, 50 μl of clodronate-liposome or control PBS-liposome (Liposoma BV, The Netherlands) was administrated intranasally to mice 2 days before arthritis induction. The depletion efficiency was assessed by flow cytometry analysis. For the in vivo Ym1 protein supplement experiment, mice were intranasally administrated with mannan to induce arthritis at day 0, and recombinant Ym1 protein (1 μg per mouse; Sino Biological Inc.) was treated intranasally at days 0, 2, and 4 after arthritis induction.
巨噬細胞清除材料和方法文獻截圖:Ym1的自然多態性通過巨噬細胞的替代性激活來調節肺炎