Abstract：
Intravenous (IV) iron nanoparticle preparations are widely used to treat iron deficiency. The mechanism of mononuclear phagocyte system-mediated clearance of IV iron nanoparticles is unknown. The early uptake and homeostasis of iron after injection of ferric carboxymaltose (FCM) in mice was studied. An increase in serum iron was observed at 2.5 h followed by a return to baseline by 24 h. An increase in circulating monocytes was observed, particularly Ly6Chi and Ly6Clow. FCM was also associated with a time-dependent decrease in liver Kupffer cells (KCs) and increase in liver monocytes. The increase in liver monocytes suggests an influx of iron-rich blood monocytes, while some KCs underwent apoptosis. Adoptive transfer experiments demonstrated that following liver infiltration, blood monocytes differentiated to KCs. KCs were also critical for IV iron uptake and biodegradation. Indeed, anti-Colony Stimulating Factor 1 Receptor (CSF1R)-mediated depletion of KCs resulted in elevated serum iron levels and impaired iron uptake by the liver. Gene expression profiling indicated that C-C chemokine receptor type 5 (CCR5) might be involved in monocyte recruitment to the liver, confirmed by pharmaceutical inhibition of CCR5. Liver KCs play a pivotal role in the clearance and storage of IV iron and KCs appear to be supported by the expanded blood monocyte population.
摘要：
静脉内(IV)铁纳米颗粒制剂广泛用于治疗铁缺乏。单核吞噬细胞系统介导的IV铁纳米颗粒清除的机制尚不清楚。研究了小鼠注射羧基麦芽糖铁（FCM）后铁的早期摄取和稳态。在2.5h时观察到血清铁的增加，然后在24h时恢复到基线。观察到循环单核细胞的增加，特别是Ly6Chi和Ly6Clow。FCM还与肝脏枯否细胞（KC）的时间依赖性减少和肝脏单核细胞的增加有关。肝脏单核细胞的增加表明富含铁的血液单核细胞流入，而一些KCs经历了凋亡。过继转移实验表明，在肝脏浸润后，血液单核细胞分化为KCs。KCs对于IV铁吸收和生物降解也至关重要。的确,抗集落刺激因子1受体(CSF1R)介导的KC耗竭导致血清铁水平升高和肝脏铁摄取受损.基因表达谱表明C-C趋化因子受体5型（CCR5）可能参与单核细胞向肝脏的募集，通过CCR5的药物抑制证实。肝脏KC在IV铁的清除和储存中起关键作用，并且KC似乎受到扩大的血液单核细胞群体的支持。
