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Lipid peroxidation regulates long-range wound detection through 5-lipoxygenase in zebrafish.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2020-08-31 , DOI: 10.1038/s41556-020-0564-2
Anushka Katikaneni 1 , Mark Jelcic 1, 2 , Gary F Gerlach 3 , Yanan Ma 1 , Michael Overholtzer 1 , Philipp Niethammer 1
Affiliation  

Rapid wound detection by distant leukocytes is essential for antimicrobial defence and post-infection survival1. The reactive oxygen species hydrogen peroxide and the polyunsaturated fatty acid arachidonic acid are among the earliest known mediators of this process2,3,4. It is unknown whether or how these highly conserved cues collaborate to achieve wound detection over distances of several hundreds of micrometres within a few minutes. To investigate this, we locally applied arachidonic acid and skin-permeable peroxide by micropipette perfusion to unwounded zebrafish tail fins. As in wounds, arachidonic acid rapidly attracted leukocytes through dual oxidase (Duox) and 5-lipoxygenase (Alox5a). Peroxide promoted chemotaxis to arachidonic acid without being chemotactic on its own. Intravital biosensor imaging showed that wound peroxide and arachidonic acid converged on half-millimetre-long lipid peroxidation gradients that promoted leukocyte attraction. Our data suggest that lipid peroxidation functions as a spatial redox relay that enables long-range detection of early wound cues by immune cells, outlining a beneficial role for this otherwise toxic process.



中文翻译:

脂质过氧化作用通过斑马鱼中的 5-脂氧合酶调节远程伤口检测。

远距离白细胞的快速伤口检测对于抗菌防御和感染后存活1至关重要。活性氧类过氧化氢和多不饱和脂肪酸花生四烯酸是该过程中最早的已知介质2,3,4. 目前尚不清楚这些高度保守的线索是否或如何协作以在几分钟内实现数百微米距离的伤口检测。为了研究这一点,我们通过微量移液管灌注局部应用花生四烯酸和皮肤渗透性过氧化物到未受伤的斑马鱼尾鳍。与伤口一样,花生四烯酸通过双重氧化酶 (Duox) 和 5-脂肪氧化酶 (Alox5a) 迅速吸引白细胞。过氧化物促进了对花生四烯酸的趋化性,而本身不具有趋化性。活体生物传感器成像显示伤口过氧化物和花生四烯酸会聚在半毫米长的脂质过氧化梯度上,从而促进白细胞的吸引力。我们的数据表明,脂质过氧化作用作为空间氧化还原中继,能够通过免疫细胞远程检测早期伤口线索,

更新日期:2020-08-31
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