Transfusion of stored blood impairs host defenses against G ram‐negative pathogens in mice
Background Although human red blood cell ( RBC ) units may be refrigerator stored for up to 42 days, transfusion of older RBC s 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...
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Published in | Transfusion (Philadelphia, Pa.) Vol. 54; no. 11; pp. 2842 - 2851 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.11.2014
|
Online Access | Get full text |
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Summary: | Background
Although human red blood cell (
RBC
) units may be refrigerator stored for up to 42 days, transfusion of older
RBC
s 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.
Study Design and Methods
To assess the effects of increased iron availability on susceptibility to infection, we infected mice with model
G
ram‐negative intracellular or extracellular pathogens (
S
almonella typhimurium
or
E
scherichia coli
, respectively), accompanied by
RBC
transfusion, iron dextran administration, or malarial coinfection.
Results
In our mouse models, transfusion of older
RBC
s exacerbates infection with both
G
ram‐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
P
lasmodium yoelii
and
S
. typhimurium
produces overwhelming
S
almonella
sepsis. Finally, treating mice with antibiotics abrogates the enhancing effect on
E
. coli
infection of both older
RBC
transfusion and iron dextran administration.
Conclusions
Transfusion of older
RBC
s exacerbates
G
ram‐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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ISSN: | 0041-1132 1537-2995 |
DOI: | 10.1111/trf.12712 |