Faculty of Medical Technology, Department of Health Science, Japan; Life Science Center, Kobe Tokiwa University, 2-6-2 Ootani-cho, Nagata-ku, Kobe 653-0838, Japan.
Faculty of Medical Technology, Department of Health Science, Japan; Life Science Center, Kobe Tokiwa University, 2-6-2 Ootani-cho, Nagata-ku, Kobe 653-0838, Japan.
Transfus Apher Sci. 2022 Apr;61(2):103319. doi: 10.1016/j.transci.2021.103319. Epub 2021 Nov 17.
In transfusion-related iron overload, haem-derived iron accumulation in monocytes/macrophages is the initial event. When iron loading exceeds the ferritin storage capacity, iron is released into the plasma. When iron loading exceeds transferrin binding capacity, labile, non-transferrin-bound iron (NTBI) appears and causes organ injury. Haemin-induced cell death has already been investigated; however, whether NTBI induces cell death in monocytes/macrophages remains unclear.
Human monocytic THP-1 cells were treated with haemin or NTBI, particularly ferric ammonium citrate (FAC) or ferrous ammonium sulfate (FAS). The intracellular labile iron pool (LIP) was measured using an iron-sensitive fluorescent probe. Ferritin expression was measured by western blotting.
LIP was elevated after haemin treatment but not after FAC or FAS treatment. Reactive oxygen species (ROS) generation and cell death induction were remarkable after haemin treatment but not after FAC or FAS treatment. Ferritin expression was not different between the FAC and haemin treatments. The combination of an iron chelator and a ferroptosis inhibitor significantly augmented the suppression of haemin cytotoxicity (p = 0.011).
The difference in LIP suggests the different iron traffic mechanisms for haem-derived iron and NTBI. The Combination of iron chelators and antioxidants is beneficial for iron overload therapy.
在输血相关的铁过载中，单核细胞/巨噬细胞中血红素衍生的铁积累是初始事件。当铁负荷超过铁蛋白的储存能力时，铁会释放到血浆中。当铁负荷超过转铁蛋白结合能力时，不稳定的、非转铁蛋白结合的铁（NTBI）出现并导致器官损伤。血红素诱导的细胞死亡已经得到了研究；然而，NTBI 是否会诱导单核细胞/巨噬细胞死亡仍不清楚。
用人单核细胞 THP-1 细胞用血红素或 NTBI 处理，特别是柠檬酸铁铵（FAC）或硫酸亚铁铵（FAS）。用铁敏感荧光探针测量细胞内可溶铁池（LIP）。通过 Western blot 测量铁蛋白表达。
血红素处理后 LIP 升高，但 FAC 或 FAS 处理后 LIP 没有升高。血红素处理后活性氧（ROS）生成和细胞死亡诱导显著，但 FAC 或 FAS 处理后没有。FAC 和血红素处理之间铁蛋白表达没有差异。铁螯合剂和铁死亡抑制剂的联合显著增强了对血红素细胞毒性的抑制（p = 0.011）。
LIP 的差异表明血红素衍生铁和 NTBI 的铁运输机制不同。铁螯合剂和抗氧化剂的联合应用有利于铁过载的治疗。
