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在巨噬细胞中激活GPR37可对感染引起的小鼠败血症和类似疼痛行为提供保护

更新时间:2025-10-18   点击次数:102次

中文摘要:

GPR37在二十多年前被发现,但其生物学功能仍然知之甚少。在这里,我们报道了GPR37在多种感染和败血症模型中的保护作用。缺失Gpr37的小鼠在受到脂多糖(LPS)、李斯特菌以及鼠疟原虫伯格氏疟原虫(Plasmodium berghei)攻击后表现出死亡率增加和/或体温下降。野生型小鼠在LPS和李斯特菌诱导的败血症中,使用青蒿琥酯(ARU)和神经保护素D1(NPD1)可以获得保护,但这些药物的保护作用在Gpr37−/−小鼠中丧失。值得注意的是,我们发现ARU可以结合巨噬细胞中的GPR37,并促进病原体的吞噬和清除。此外,巨噬细胞通过荷兰Liposoma的巨噬细胞清除剂来清除会加重感染、败血症及其后续影响,而采用NPD1或ARU诱导的巨噬细胞移植可以降低感染、败血症和类疼痛行为。我们的研究揭示了ARU通过激活巨噬细胞在宿主细胞中的生理作用,并提示GPR37激动剂可能有助于治疗败血症、细菌感染和疟疾。


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.


论文信息:

论文题目:Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice

期刊名称:Nature Communications

时间期卷:12, Article number: 1704 (2021)

在线时间:2021年3月17日

DOI:doi.org/10.1038/s41467-021-21940-8


  

产品信息:

货号:CP-005-005

规格:5ml+5ml

品牌:Liposoma

产地:荷兰

名称:Clodronate Liposomes

办事处:Target Technology(靶点科技)


Clodronate Liposomes氯膦酸盐脂质体清除腹腔巨噬细胞,疾病模型为:脂多糖(LPS)、李斯特菌以及鼠疟原虫伯格氏疟原虫(Plasmodium berghei)攻击。荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications:在巨噬细胞中激活GPR37可对感染引起的小鼠败血症和类似疼痛行为提供保护.

在巨噬细胞中激活GPR37可对感染引起的小鼠败血症和类似疼痛行为提供保护


Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法:

Cell depletion

Reagents

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.


材料和方法文献截图:

在巨噬细胞中激活GPR37可对感染引起的小鼠败血症和类似疼痛行为提供保护


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