Transfusion of stored blood impairs host defenses against Gram-negative pathogens in mice.
Transfusion of stored blood impairs host defenses against Gram-negative pathogens in mice.
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作者：
Prestia K;Bandyopadhyay S;Slate A;Francis RO;Francis KP;Spitalnik SL;Fidock DA;Brittenham GM;Hod EA
虽然人红细胞（RBC）单位可以在冰箱中保存长达42天，但输入较老的红细胞会给单核吞噬细胞带来大量铁。同样，右旋糖酐铁在血浆中循环数小时至数天，逐渐被单核吞噬细胞清除，并将铁返回血浆。最后，疟疾感染通过血管内和血管外溶血持续向巨噬细胞输送铁。研究表明，服用铁会增加感染风险。为了评估铁供应增加对感染易感性的影响，我们用模型革兰氏阴性细胞内或细胞外病原体（分别为鼠伤寒沙门菌或大肠杆菌）感染小鼠，并伴有红细胞输血、右旋糖酐铁或疟疾合并感染。在我们的小鼠模型中，老年红细胞的输血加剧了革兰氏阴性病原体的感染。虽然右旋糖酐铁加重大肠杆菌感染的程度与输入相应数量的铁相似，但需要更高剂量的铁才能产生与鼠伤寒沙门氏菌相当的效果。同时感染约尔氏疟原虫和鼠伤寒沙门氏菌的小鼠产生压倒性的沙门氏菌败血症。最后，用抗生素治疗小鼠可消除老年红细胞输注和右旋糖酐铁对大肠杆菌感染的增强作用。输血老年红细胞加重革兰氏阴性感染的程度与疟疾合并感染或右旋糖酐铁治疗的程度相似。适当的抗生素治疗可消除老年红细胞输注对大肠杆菌感染的影响。铁传递到巨噬细胞可能是一个被低估的机制，介导，至少一些，红细胞输注的不良反应。
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.
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影响因子：
--
作者：
GRIMES, AJ;HUTT, MSR
通讯作者：
HUTT, MSR
影响因子：
6.5
作者：
NOYES, WD;BOTHWELL, TH;FINCH, CA
通讯作者：
FINCH, CA
DOI：
10.1016/s0035-9203(99)90024-x
发表时间：
1999-05-01
影响因子：
2.2
作者：
Berkley, J;Mwarumba, S;Marsh, K
通讯作者：
Marsh, K
影响因子：
3.1
作者：
Juffermans, Nicole P.;Prins, David J.;Binnekade, Jan M.
通讯作者：
Binnekade, Jan M.
DOI：
10.1016/s0035-9203(99)90282-1
发表时间：
1999-03-01
影响因子：
2.2
作者：
Ammah, A;Nkuo-Akenji, T;Deas, JE
通讯作者：
Deas, JE