Live Imaging Reveals Differing Roles of Macrophages and Neutrophils during Zebrafish Tail Fin Regeneration

Live Imaging Reveals Differing Roles of Macrophages and Neutrophils during Zebrafish Tail Fin Regeneration
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实时成像揭示巨噬细胞和中性粒细胞在斑马鱼尾鳍再生过程中的不同作用

DOI:
10.1074/jbc.m112.349126
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发表时间:
2012-07-20
影响因子:
4.8
通讯作者:
Wen, Zi-Long
Wen, Zi-Long
中科院分区:
生物学2区
文献类型:
--
作者:
Li, Li;Yan, Bo;Wen, Zi-Long

文献摘要

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巨噬细胞和中性粒细胞是关键的免疫吞噬细胞,它们在组织损伤后进入伤口以清除细胞碎片和侵入的微生物,这可能促进损伤组织的再生长。利用斑马鱼的再生能力和新产生的白细胞特异性斑马鱼系与白细胞谱系的标记,我们评估了中性粒细胞和巨噬细胞在尾鳍再生过程中的行为和功能。活体成像显示,在截肢后6小时内,即炎症阶段,中性粒细胞是清除凋亡小体和小细胞碎片的主要细胞,尽管它们具有有限的吞噬能力并迅速经历凋亡。从截肢后6小时开始,即消退和再生阶段,巨噬细胞成为主要的清道夫,有效地解决炎症并促进组织重塑和再生。消融巨噬细胞而非中性粒细胞严重损害了炎症消退和组织再生,导致再生鳍中形成大空泡。相比之下,去除中性粒细胞略微加速了受损鳍的再生。我们的研究记录了巨噬细胞和中性粒细胞在组织再生过程中的不同行为和功能。
Macrophages and neutrophils are the pivotal immune phagocytes that enter the wound after tissue injury to remove the cell debris and invaded microorganisms, which presumably facilitate the regrowth of injured tissues. Taking advantage of the regeneration abilities of zebrafish and the newly generated leukocyte-specific zebrafish lines with labeling of both leukocyte lineages, we assessed the behaviors and functions of neutrophils and macrophages during tail fin regeneration. Live imaging showed that within 6 hours post amputation, the inflammatory stage, neutrophils were the primary cells scavenging apoptotic bodies and small cell debris, although they had limited phagocytic capacity and quickly underwent apoptosis. From 6 hours post amputation on, the resolution and regeneration stage, macrophages became the dominant scavengers, efficiently resolving inflammation and facilitating tissue remodeling and regrowth. Ablation of macrophages but not neutrophils severely impaired the inflammatory resolution and tissue regeneration, resulting in the formation of large vacuoles in the regenerated fins. In contrast, removal of neutrophils slightly accelerates the regrowth of injured fin. Our study documents the differing behaviors and functions of macrophages and neutrophils during tissue regeneration.