Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, University of Hull, Hull.
Hull and East Yorkshire Hospitals National Health Service Trust, Hull.
Am J Pathol. 2019 Nov;189(11):2196-2208. doi: 10.1016/j.ajpath.2019.07.015. Epub 2019 Aug 27.
Macrophages are important for effective iron recycling and erythropoiesis, but they also play a crucial role in wound healing, orchestrating tissue repair. Recently, we demonstrated a significant accumulation of iron in healing wounds and a requirement of iron for effective repair. Herein, we sought to determine the influence of iron on macrophage function in the context of wound healing. Interestingly, wound macrophages extensively sequestered iron throughout healing, associated with a prohealing M2 phenotype. In delayed healing diabetic mouse wounds, both macrophage polarization and iron sequestration were impaired. In vitro studies revealed that iron promotes differentiation, while skewing macrophages toward a hypersecretory M2-like polarization state. These macrophages produced high levels of chemokine (C-C motif) ligands 17 and 22, promoting wound reepithelialization and extracellular matrix deposition in a human ex vivo wound healing model. Together, these findings reveal a novel, unappreciated role for iron in modulating macrophage behavior to promote subsequent wound repair. These findings support therapeutic evaluation of iron use to promote wound healing in the clinic.
巨噬细胞对于有效的铁回收和红细胞生成至关重要，但它们在伤口愈合中也起着关键作用，协调组织修复。最近，我们证明了在愈合的伤口中有大量铁的积累，并且铁对有效修复是必需的。在此，我们试图确定铁在伤口愈合背景下对巨噬细胞功能的影响。有趣的是，伤口巨噬细胞在整个愈合过程中广泛地摄取铁，与促进愈合的 M2 表型相关。在延迟愈合的糖尿病小鼠伤口中，巨噬细胞极化和铁摄取都受损。体外研究表明，铁促进分化，同时使巨噬细胞向过度分泌的 M2 样极化状态倾斜。这些巨噬细胞产生高水平的趋化因子（C-C 基序）配体 17 和 22，促进人离体伤口愈合模型中的伤口再上皮化和细胞外基质沉积。总之，这些发现揭示了铁在调节巨噬细胞行为以促进随后的伤口修复中的一个新的、未被认识的作用。这些发现支持在临床上评估铁的使用以促进伤口愈合的治疗。
