中文摘要:
GPR37在二十多年前被發現,但其生物學功能仍然知之甚少。在這里,我們報道了GPR37在多種感染和敗血癥模型中的保護作用。缺失Gpr37的小鼠在受到脂多糖(LPS)、李斯特菌以及鼠瘧原蟲伯格氏瘧原蟲(Plasmodium berghei)攻擊后表現出死亡率增加和/或體溫下降。野生型小鼠在LPS和李斯特菌誘導的敗血癥中,使用青蒿琥酯(ARU)和神經保護素D1(NPD1)可以獲得保護,但這些藥物的保護作用在Gpr37?/?小鼠中喪失。值得注意的是,我們發現ARU可以結合巨噬細胞中的GPR37,并促進病原體的吞噬和清除。此外,巨噬細胞通過荷蘭Liposoma的巨噬細胞清除劑來清除會加重感染、敗血癥及其后續影響,而采用NPD1或ARU誘導的巨噬細胞移植可以降低感染、敗血癥和類疼痛行為。我們的研究揭示了ARU通過激活巨噬細胞在宿主細胞中的生理作用,并提示GPR37激動劑可能有助于治療敗血癥、細菌感染和瘧疾。
英文摘要:
GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37?/? mice. Notably, we found that ARU binds to GPR37 in macrophages and promotes phagocytosis and clearance of pathogens. Moreover, ablation of macrophages potentiated infection, sepsis, and their sequelae, whereas adoptive transfer of NPD1- or ARU-primed macrophages reduced infection, sepsis, and pain-like behaviors. Our findings reveal physiological actions of ARU in host cells by activating macrophages and suggest that GPR37 agonists may help to treat sepsis, bacterial infections, and malaria.
論文信息:
論文題目:Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice
期刊名稱:Nature Communications
時間期卷:12, Article number: 1704 (2021)
在線時間:2021年3月17日
DOI:doi.org/10.1038/s41467-021-21940-8
產品信息:
貨號:CP-005-005
規格:5ml+5ml
品牌:Liposoma
產地:荷蘭
名稱:Clodronate Liposomes
辦事處:Target Technology(靶點科技)
Clodronate Liposomes氯膦酸鹽脂質體清除腹腔巨噬細胞,疾病模型為:脂多糖(LPS)、李斯特菌以及鼠瘧原蟲伯格氏瘧原蟲(Plasmodium berghei)攻擊。荷蘭Liposoma巨噬細胞清除劑Clodronate Liposomes見刊于Nature Communications:在巨噬細胞中激活GPR37可對感染引起的小鼠敗血癥和類似疼痛行為提供保護.
Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體的材料和方法:
We obtained the following reagents from the indicated sources/vendors: pHrodo® Red Zymosan Bioparticles® Conjugate (Thermo Scientific; P35364, 1?mg/ml PBS stock), pHrodo® Red AM (Thermo Scientific; P35372, 10 mM DMSO stock), natural drug library (Selleckchem; L1400, 10?mM DMSO stock, see Supplementary Table 1 for drugs tested), LC3 detection dye (Dojindo Molecular Technologies, Inc.; D675-10), ROS/RNS kit (ENZO Life Science; ENZ-51001-200), artesunate (Cayman Chemicals; 11817, 30?mM DMSO stock), artemisinin (Cayman Chemicals; 11816, 30?mM DMSO stock), dihydroartemisinin (Abcam; ab142690, 30?mM DMSO stock), and clodronate liposomes (Liposoma B.V.; C-005). NPD1 was gifted from Resolvyx Pharmaceuticals. All reagents were used in the dose and manner described in the figure legends.
材料和方法文獻截圖: