Kaveh Aryan, Bruton Finnius A, Buckley Charlotte, Oremek Magdalena E M, Tucker Carl S, Mullins John J, Taylor Jonathan M, Rossi Adriano G, Denvir Martin A
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Front Cell Dev Biol. 2020 Oct 19;8:579943. doi: 10.3389/fcell.2020.579943. eCollection 2020.
Neutrophils and macrophages are crucial effectors and modulators of repair and regeneration following myocardial infarction, but they cannot be easily observed in mammalian models. Hence many studies have utilized larval zebrafish injury models to examine neutrophils and macrophages in their tissue of interest. However, to date the migratory patterns and ontogeny of these recruited cells is unknown. In this study, we address this need by comparing our larval zebrafish model of cardiac injury to the archetypal tail fin injury model. Our imaging allowed comprehensive mapping of neutrophil and macrophage migration from primary hematopoietic sites, to the wound. Early following injury there is an acute phase of neutrophil recruitment that is followed by sustained macrophage recruitment. Both cell types are initially recruited locally and subsequently from distal sites, primarily the caudal hematopoietic tissue (CHT). Once liberated from the CHT, some neutrophils and macrophages enter circulation, but most use abluminal vascular endothelium to crawl through the larva. In both injury models the innate immune response resolves by reverse migration, with very little apoptosis or efferocytosis of neutrophils. Furthermore, our imaging led to the finding of a novel wound responsive + neutrophil subset, highlighting previously unrecognized heterogeneity in neutrophils. Our study provides a detailed analysis of the modes of immune cell migration in larval zebrafish, paving the way for future studies examining tissue injury and inflammation.
中性粒细胞和巨噬细胞是心肌梗死后修复和再生的关键效应细胞和调节细胞，但在哺乳动物模型中难以轻易观察到它们。因此，许多研究利用斑马鱼幼体损伤模型来研究目标组织中的中性粒细胞和巨噬细胞。然而，迄今为止，这些募集细胞的迁移模式和个体发生情况尚不清楚。在本研究中，我们通过将我们的斑马鱼幼体心脏损伤模型与典型的尾鳍损伤模型进行比较来满足这一需求。我们的成像能够全面描绘中性粒细胞和巨噬细胞从主要造血部位迁移到伤口的过程。损伤后早期有一个中性粒细胞募集的急性期，随后是持续的巨噬细胞募集。两种细胞类型最初都是在局部募集，随后从远端部位募集，主要是尾造血组织（CHT）。一旦从中性粒细胞募集的急性期，随后是持续的巨噬细胞募集。两种细胞类型最初都是在局部募集，随后从远端部位募集，主要是尾造血组织（CHT）。一旦从CHT释放出来，一些中性粒细胞和巨噬细胞进入循环，但大多数利用血管腔外的血管内皮在幼体中爬行。在两种损伤模型中，先天性免疫反应都通过反向迁移消退，中性粒细胞很少发生凋亡或被吞噬。此外，我们的成像发现了一种新的伤口反应性中性粒细胞亚群，突出了中性粒细胞中以前未被认识到的异质性。我们的研究对斑马鱼幼体中免疫细胞迁移模式进行了详细分析，为未来研究组织损伤和炎症铺平了道路。
