Prestia Kevin, Bandyopadhyay Sheila, Slate Andrea, Francis Richard O, Francis Kevin P, Spitalnik Steven L, Fidock David A, Brittenham Gary M, Hod Eldad A
Institute of Comparative Medicine, Columbia University Medical Center-New York Presbyterian Hospital, New York, New York; Department of Pathology and Cell Biology, Columbia University Medical Center-New York Presbyterian Hospital, New York, New York.
Transfusion. 2014 Nov;54(11):2842-51. doi: 10.1111/trf.12712. Epub 2014 May 19.
Although human red blood cell (RBC) units may be refrigerator stored for up to 42 days, transfusion of older RBCs acutely delivers a large bolus of iron to mononuclear phagocytes. Similarly, iron dextran circulates in plasma for hours to days and is progressively cleared by mononuclear phagocytes, which return iron to plasma. Finally, malaria infection continuously delivers iron to macrophages by intra- and extravascular hemolysis. Studies suggest that iron administration increases infectious risk.
To assess the effects of increased iron availability on susceptibility to infection, we infected mice with model Gram-negative intracellular or extracellular pathogens (Salmonella typhimurium or Escherichia coli, respectively), accompanied by RBC transfusion, iron dextran administration, or malarial coinfection.
In our mouse models, transfusion of older RBCs exacerbates infection with both Gram-negative pathogens. Although iron dextran exacerbates E. coli infection to a similar extent as transfusion of corresponding amounts of iron, higher iron doses are required to produce comparable effects with S. typhimurium. Coinfection of mice with Plasmodium yoelii and S. typhimurium produces overwhelming Salmonella sepsis. Finally, treating mice with antibiotics abrogates the enhancing effect on E. coli infection of both older RBC transfusion and iron dextran administration.
Transfusion of older RBCs exacerbates Gram-negative infection to a similar extent as malaria coinfection or iron dextran administration. Appropriate antibiotic therapy abrogates the effect of older RBC transfusions on infection with E. coli. Iron delivery to macrophages may be an underappreciated mechanism mediating, at least some, adverse effects of RBC transfusions.
尽管人类红细胞（RBC）单位可在冰箱中储存长达42天，但输注较陈旧的红细胞会急性地将大量铁传递给单核吞噬细胞。同样，右旋糖酐铁在血浆中循环数小时至数天，并逐渐被单核吞噬细胞清除，单核吞噬细胞将铁返还至血浆。最后，疟疾感染通过血管内和血管外溶血持续将铁传递给巨噬细胞。研究表明，给予铁会增加感染风险。
为了评估铁供应增加对感染易感性的影响，我们用革兰氏阴性细胞内或细胞外病原体模型（分别为鼠伤寒沙门氏菌或大肠杆菌）感染小鼠，同时进行红细胞输注、给予右旋糖酐铁或合并疟疾感染。
在我们的小鼠模型中，输注较陈旧的红细胞会加重两种革兰氏阴性病原体的感染。尽管右旋糖酐铁加重大肠杆菌感染的程度与输注相应量铁的程度相似，但需要更高剂量的铁才能对鼠伤寒沙门氏菌产生类似效果。约氏疟原虫和鼠伤寒沙门氏菌合并感染小鼠会导致严重的沙门氏菌败血症。最后，用抗生素治疗小鼠可消除较陈旧红细胞输注和给予右旋糖酐铁对大肠杆菌感染的增强作用。
输注较陈旧的红细胞加重革兰氏阴性感染的程度与合并疟疾感染或给予右旋糖酐铁相似。适当的抗生素治疗可消除较陈旧红细胞输注对大肠杆菌感染的影响。向巨噬细胞传递铁可能是介导红细胞输注至少部分不良反应的一种未得到充分认识的机制。
