斑马鱼伤口愈合过程中巨噬细胞经历行为转变,Free Radical Biology and Medicine

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斑马鱼伤口愈合过程中巨噬细胞经历行为转变
Free Radical Biology and Medicine ( IF 7.1 ) Pub Date : 2022-09-24 , DOI: 10.1016/j.freeradbiomed.2022.09.021
Tamara Sipka ₁ , Seol Ah Park ₂ , Resul Ozbilgic ₁ , Laurence Balas ₃ , Thierry Durand ₃ , Karol Mikula ₂ , Georges Lutfalla ₁ , Mai Nguyen-Chi ₁

Affiliation

为了响应伤口信号，巨噬细胞立即被招募到损伤处，在那里它们获得独特的表型和功能，在宿主防御和愈合过程中发挥关键作用。尽管在伤口愈合过程中巨噬细胞表型已得到深入研究，主要使用标记物和表达谱，但伤口环境对巨噬细胞形状和行为的影响以及潜在机制值得更深入的研究。在这里，我们试图描述斑马鱼幼虫尾鳍折叠无菌损伤期间巨噬细胞招募和行为的动态特征。使用光转换方法，我们证明巨噬细胞以单波的形式被招募到受伤的鳍褶处，在那里它们改变了表型。巨噬细胞形状和轨迹的活体成像显示，伤口巨噬细胞表现出一组高度刻板的行为，并随着伤口愈合的进行，将其形状从变形虫形状改变为拉长形状。使用 15-脂氧合酶的药理学抑制剂和保护素 D1（一种专门的促溶解脂质），我们研究了多不饱和脂肪酸代谢在巨噬细胞行为中的作用。虽然使用 PD146176 或去甲二氢愈创木酸 (NDGA) 抑制 15-脂氧合酶会减少阿米巴形向拉长形状的转变，但保护素 D1 会加速巨噬细胞反向迁移并有利于拉长形态。总而言之，我们的研究结果表明，伤口处的单个巨噬细胞会改变其表型，导致行为和形状发生重要变化，以适应不断变化的环境，并强调脂质代谢在炎症期间控制巨噬细胞行为可塑性中的关键作用。

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Macrophages undergo a behavioural switch during wound healing in zebrafish

In response to wound signals, macrophages are immediately recruited to the injury where they acquire distinct phenotypes and functions, playing crucial roles both in host defense and healing process. Although macrophage phenotypes have been intensively studied during wound healing, mostly using markers and expression profiles, the impact of the wound environment on macrophage shape and behaviour, and the underlying mechanisms deserve more in-depth investigation. Here, we sought to characterize the dynamics of macrophage recruitment and behaviour during aseptic wounding of the caudal fin fold of the zebrafish larva. Using a photo-conversion approach, we demonstrated that macrophages are recruited to the wounded fin fold as a single wave where they switch their phenotype. Intravital imaging of macrophage shape and trajectories revealed that wound-macrophages display a highly stereotypical set of behaviours and change their shape from amoeboid to elongated shape as wound healing proceeds. Using a pharmacological inhibitor of 15-lipoxygenase and protectin D1, a specialized pro-resolving lipid, we investigated the role of polyunsaturated fatty acid metabolism in macrophage behaviour. While inhibition of 15-lipoxygenase using PD146176 or Nordihydroguaiaretic acid (NDGA) decreases the switch from amoeboid to elongated shape, protectin D1 accelerates macrophage reverse migration and favours elongated morphologies. Altogether, our findings suggest that individual macrophages at the wound switch their phenotype leading to important changes in behaviour and shape to adapt to changing environment, and highlight the crucial role of lipid metabolism in the control of macrophage behaviour plasticity during inflammation .

更新日期：2022-09-24

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