Loss of red cell chemokine scavenging promotes transfusion-related lung inflammation
Loss of red cell chemokine scavenging promotes transfusion-related lung inflammation
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DOI：
10.1182/blood-2008-07-166264
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发表时间：
2009-01-29
期刊：
影响因子：
20.3
通讯作者：
Lee, Janet S.
中科院分区：
文献类型：
--
作者：
Mangalmurti, Nilam S.;Xiong, Zeyu;Lee, Janet S.
红细胞输注与危重病人急性肺损伤的发生有关。最近的证据表明，储存引起的红细胞（RBC）的改变统称为“储存损伤”，可能与不良的生物学后果有关。利用2事件模型，我们研究了来自同源C57BL/6小鼠的纯化红细胞浓缩物是否会改变小鼠肺部的炎症反应。与输注不足1天的红细胞相比，输注储存10天的红细胞增加了空气中中性粒细胞计数、巨噬细胞炎症蛋白-2 （MIP-2）和趋化因子（KC）浓度以及肺微血管通透性。由于红细胞已被证明可以通过血型Duffy抗原清除炎症趋化因子，我们研究了Duffy抗原在储存过程中的表达和功能。在储存的人红细胞中，Duffy表达和趋化因子清除功能随着储存时间的增加而降低。将Duffy敲除红细胞输注到Duffy野生型内毒素小鼠中，与输注Duffy野生型红细胞相比，增加了空气中性粒细胞、炎症细胞因子浓度和肺微血管通透性。因此，红细胞趋化因子清除的减少是储存损伤的一个功能后果，红细胞输血可以增强现有的肺部炎症。(血。2009;113:1158 - 1166)
Red cell transfusions are associated with the development of acute lung injury in the critically ill. Recent evidence suggests that storage induced alterations of the red blood cell (RBC) collectively termed the "storage lesion" may be linked with adverse biologic consequences. Using a 2-event model of systemic endotoxemia followed by a secondary challenge of RBC transfusion, we investigated whether purified RBC concentrates from syngeneic C57BL/6 mice altered inflammatory responses in murine lungs. Transfusion of RBCs stored for 10 days increased neutrophil counts, macrophage inflammatory protein-2 (MIP-2) and chemokine (KC) concentrations in the airspaces, and lung microvascular permeability compared with transfusion of less than 1-day-old RBCs. Because RBCs have been shown to scavenge inflammatory chemokines through the blood group Duffy antigen, we investigated the expression and function of Duffy during storage. In banked human RBCs, both Duffy expression and chemokine scavenging function were reduced with increasing duration of storage. Transfusion of Duffy knockout RBCs into Duffy wild-type endotoxemic mice increased airspace neutrophils, inflammatory cytokine concentrations, and lung microvascular permeability compared with transfusion of Duffy wild-type RBCs. Thus, reduction in erythrocyte chemokine scavenging is one functional consequence of the storage lesion by which RBC transfusion can augment existing lung inflammation. (Blood. 2009;113:1158-1166)