在巨噬細(xì)胞中激活GPR37可對(duì)感染引起的小鼠敗血癥和類似疼痛行為提供保護(hù)

中文摘要：

GPR37在二十多年前被發(fā)現(xiàn)，但其生物學(xué)功能仍然知之甚少。在這里，我們報(bào)道了GPR37在多種感染和敗血癥模型中的保護(hù)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(xiàn)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(dǎo)的敗血癥中，使用青蒿琥酯（ARU）和神經(jīng)保護(hù)素D1（NPD1）可以獲得保護(hù)，但這些藥物的保護(hù)作用在Gpr37?/?小鼠中喪失。值得注意的是，我們發(fā)現(xiàn)ARU可以結(jié)合巨噬細(xì)胞中的GPR37，并促進(jìn)病原體的吞噬和清除。此外，巨噬細(xì)胞通過荷蘭Liposoma的巨噬細(xì)胞清除劑來清除會(huì)加重感染、敗血癥及其后續(xù)影響，而采用NPD1或ARU誘導(dǎo)的巨噬細(xì)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(xì)胞在宿主細(xì)胞中的生理作用，并提示GPR37激動(dòng)劑可能有助于治療敗血癥、細(xì)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(shí)間期卷：12, Article number: 1704 (2021)

在線時(shí)間：2021年3月17日

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

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes

辦事處：Target Technology(靶點(diǎn)科技)

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除腹腔巨噬細(xì)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(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：在巨噬細(xì)胞中激活GPR37可對(duì)感染引起的小鼠敗血癥和類似疼痛行為提供保護(hù).

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

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.

材料和方法文獻(xiàn)截圖：