Imaging Program, Lawson Health Research Institute, London, ON N6A 4V2, Canada.
Medical Biophysics, Western University, London, ON N6A 5C1, Canada.
Int J Mol Sci. 2023 Feb 17;24(4):4036. doi: 10.3390/ijms24044036.
Many chronic inflammatory conditions are mediated by an increase in the number of monocytes in peripheral circulation, differentiation of monocytes to macrophages, and different macrophage subpopulations during pro- and anti-inflammatory stages of tissue injury. When hepcidin secretion is stimulated during inflammation, the iron export protein ferroportin is targeted for degradation on a limited number of cell types, including monocytes and macrophages. Such changes in monocyte iron metabolism raise the possibility of non-invasively tracking the activity of these immune cells using magnetic resonance imaging (MRI). We hypothesized that hepcidin-mediated changes in monocyte iron regulation influence both cellular iron content and MRI relaxation rates. In response to varying conditions of extracellular iron supplementation, ferroportin protein levels in human THP-1 monocytes decreased two- to eightfold, consistent with paracrine/autocrine regulation of iron export. Following hepcidin treatment, ferroportin protein levels further decreased two- to fourfold. This was accompanied by an approximately twofold increase in total transverse relaxation rate, R*, compared to non-supplemented cells. A positive correlation between total cellular iron content and R* improved from moderate to strong in the presence of hepcidin. These findings suggest that hepcidin-mediated changes detected in monocytes using MRI could be valuable for in vivo cell tracking of inflammatory responses.
许多慢性炎症性疾病是由外周循环中单核细胞数量增加、单核细胞向巨噬细胞分化以及组织损伤的促炎和抗炎阶段不同的巨噬细胞亚群引起的。当炎症期间铁调素分泌受到刺激时，铁输出蛋白亚铁转运蛋白在包括单核细胞和巨噬细胞在内的少数几种细胞类型上被靶向降解。单核细胞铁代谢的这种变化使得使用磁共振成像 (MRI) 非侵入性地跟踪这些免疫细胞的活性成为可能。我们假设铁调素介导的单核细胞铁调节变化影响细胞内铁含量和 MRI 弛豫率。在对外源性铁补充条件进行不同的条件下，人 THP-1 单核细胞中的亚铁转运蛋白蛋白水平降低了 2 到 8 倍，这与铁输出的旁分泌/自分泌调节一致。在铁调素处理后，亚铁转运蛋白蛋白水平进一步降低了 2 到 4 倍。这伴随着总横向弛豫率 R* 大约增加了两倍，与未补充细胞相比。铁调素存在时，总细胞内铁含量与 R* 之间的相关性从中度改善为强相关。这些发现表明，使用 MRI 在单核细胞中检测到的铁调素介导的变化可能对炎症反应的体内细胞跟踪很有价值。
