Oxoeicosanoid signaling mediates early antimicrobial defense in zebrafish.
Oxoeicosanoid signaling mediates early antimicrobial defense in zebrafish.
复制标题
DOI：
10.1016/j.celrep.2022.111974
复制
发表时间：
2023-01-31
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
5-oxoETE 是一种生物活性脂质，源自磷脂酶 A2 激活与氧化应激同时产生的花生四烯酸。通过其 G 蛋白偶联受体 OXER1，纯 5-oxoETE 是一种有效的白细胞趋化剂。然而，由于不寻常的 OXER1 保守模式，其生理功能仍然难以捉摸。 OXER1从鱼类到灵长类动物都是保守的，但在啮齿类动物中则不然，这排除了在小鼠中进行遗传功能丧失的研究。为了确定其生理作用，我们将转录组学、脂质组学和活体成像测定与斑马鱼中 OXER1 直系同源物 hcar1-4 的遗传扰动结合起来。铜绿假单胞菌感染诱导 5-oxoETE 及其受体的合成，以及其他炎症途径。 Hcar1-4 缺失会减弱中性粒细胞的募集并降低感染后存活率，这可以通过 hcar1-4 或人 OXER1 的异位表达来挽救。通过揭示 5-oxoETE 作为非啮齿动物脊椎动物早期抗菌反应的主要脂质调节剂，我们的工作扩展了当前以啮齿动物为中心的早期炎症观点。 5-oxoETE 是一种源自花生四烯酸的炎性脂质。 5-oxoETE 的生理功能知之甚少，部分原因是其 G 蛋白偶联受体 OXER1 没有已知的啮齿动物直系同源物。在这里，马等人。使用表达 OXER1 直系同源物的斑马鱼来阐明该途径在针对细菌感染的快速先天免疫防御中的基本生理功能。
5-oxoETE is a bioactive lipid derived from arachidonic acid generated when phospholipase A2 activation coincides with oxidative stress. Through its G protein-coupled receptor OXER1, pure 5-oxoETE is a potent leukocyte chemoattractant. Yet, its physiological function has remained elusive owing to the unusual OXER1 conservation pattern. OXER1 is conserved from fish to primates but not in rodents, precluding genetic loss-of-function studies in mouse. To determine its physiological role, we combine transcriptomic, lipidomic, and intravital imaging assays with genetic perturbations of the OXER1 ortholog hcar1–4 in zebrafish. Pseudomonas aeruginosa infection induces the synthesis of 5-oxoETE and its receptor, along with other inflammatory pathways. Hcar1–4 deletion attenuates neutrophil recruitment and decreases post-infection survival, which could be rescued by ectopic expression of hcar1–4 or human OXER1. By revealing 5-oxoETE as dominant lipid regulator of the early antimicrobial response in a non-rodent vertebrate, our work expands the current, rodent-centric view of early inflammation. 5-oxoETE is an inflammatory lipid derived from arachidonic acid. 5-oxoETE’s physiological functions are little understood, partly because its G protein-coupled receptor, OXER1, has no known rodent orthologs. Here, Ma et al. use zebrafish, which express OXER1 orthologs, to illuminate the pathway’s essential physiological functions in rapid innate immune defense against bacterial infection.
登录
查看更多内容
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
21.3
作者：
Enyedi, Balazs;Kala, Snigdha;Niethammer, Philipp
通讯作者：
Niethammer, Philipp
影响因子：
1.2
作者：
Benard, Erica L.;van der Sar, Astrid M.;Meijer, Annemarie H.
通讯作者：
Meijer, Annemarie H.
DOI：
10.1073/pnas.0712195105
发表时间：
2008-02-19
影响因子：
11.1
作者：
Bolcome, Robert E., III;Sullivan, Sarah E.;Chan, Joanne
通讯作者：
Chan, Joanne