Changes in function of iron-loaded alveolar macrophages after in vivo administration of desferrioxamine and/or chloroquine
Changes in function of iron-loaded alveolar macrophages after in vivo administration of desferrioxamine and/or chloroquine
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DOI：
10.1016/s0162-0134(02)00633-5
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发表时间：
2003-02-01
影响因子：
3.9
通讯作者：
Crichton, RR
中科院分区：
文献类型：
--
作者：
Legssyer, R;Josse, C;Crichton, RR
去铁胺 (DFO) 和氯喹均可分别通过螯合低分子量池中的铁或减少转铁蛋白-转铁蛋白受体循环的铁摄取，显着降低铁过载实验动物的肝铁含量。然而，之前没有研究调查这两种药物的联合治疗是否会进一步降低组织铁过载以及铁引起的毒性。在铁负荷方案（10 mg/kg，3x/周）期间，向大鼠施用氯喹（15 mg/kg，5x/周），持续 4 周，显着降低肝脏（54%）和巨噬细胞铁含量（24%）。然而，当铁负荷停止时与去铁胺（10 mg/kg，3x/周）联合用药，持续两周，没有发现肝脏铁含量进一步降低，而巨噬细胞的铁含量显着增加，可能表明铁胺通过这些细胞的流量。有必要进一步研究这些巨噬细胞内铁的形态。与铁负荷巨噬细胞中的这些参数相比，从氯喹治疗的铁负荷大鼠中分离的巨噬细胞显示潜在的 NFkappaB 激活减少，脂多糖刺激的亚硝酸盐释放显着增加。氯喹和去铁胺的共同给药使 NFkappaB 的潜在活性正常化为对照巨噬细胞的潜在活性，并且增加 LPS 刺激的 NO 释放至对照值。然而，单独使用 DFO 对这些参数均没有任何显着影响。这些结果可能与从接受螯合治疗的地中海贫血患者中分离出的载铁巨噬细胞的免疫功能降低及其感染增加的倾向具有重要相关性。 (C) 2002 Elsevier Science Inc. 保留所有权利。
Both desferrioxamine (DFO) and chloroquine can significantly reduce hepatic iron in experimental animals with iron overload by chelating iron from the low-molecular-weight pool or decreasing iron uptake by the transferrin-transferrin receptor cycle, respectively. However, no previous studies have investigated whether combination therapy of these two drugs would further decrease the tissue iron overload as well as iron-induced toxicity. Chloroquine administration, 15 mg/kg, 5x/week, to rats during the iron loading regime, 10 mg/kg, 3x/week for 4 weeks, significantly decreased both hepatic (54%) and macrophage iron content (24%). However when administered in combination with desferrioxamine, 10 mg/kg, 3x/week for 2 weeks at the cessation of iron loading, no further reduction of hepatic iron content was noted while the iron content of the macrophages significantly increased, possibly indicating the flux of ferrioxamine through these cells. Further studies are warranted to investigate the speciation of iron within these macrophages. Macrophages isolated from chloroquine-treated iron loaded rats showed a reduction in latent NFkappaB activation and a significant increase in lipopolysaccharide-stimulated nitrite release by comparison to these parameters in iron loaded macrophages. Co-administration of chloroquine and desferrioxamine normalised the latent activity of NFkappaB to that of control macrophages as well as increasing LPS-stimulated NO release towards control values. However, DFO alone did not have any significant effect upon either of these parameters. Such results may have important relevance for the reduced immune function of iron loaded macrophages isolated from thalassaemia patients receiving chelation therapy and their propensity to increased infection. (C) 2002 Elsevier Science Inc. All rights reserved.