Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion-related acute lung injury
Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion-related acute lung injury
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DOI：
10.1182/blood-2006-04-017251
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发表时间：
2006-10-01
期刊：
影响因子：
20.3
通讯作者：
Silliman, Christopher C.
中科院分区：
文献类型：
--
作者：
Khan, Samina Yasmin;Kelher, Marguerite R.;Silliman, Christopher C.
输血相关急性肺损伤（TRALI）是输血后急性肺功能不全的一种形式，与输注生物反应调节剂（BRM）有关，包括抗白细胞抗体和脂质。可溶性CD 40配体（sCD 40 L）是血小板源性促炎介质，在血小板储存期间积累。我们假设人多形核白细胞（PMNs）表达CD 40，CD 40连接快速启动PMNs，sCD 40 L诱导PMNs介导的人肺微血管内皮细胞（HMVECs）的细胞毒性。在TRALI或未引起输血反应的对照PC涉及的血液成分和血小板浓缩物（PC）中测量sCD 40 L水平。所有血液成分的sCD 40 L水平均高于新鲜血浆，单采血液成分PC的sCD 40 L浓度最高，其次是来自全血、全血和浓缩红细胞（PRBC）的PC。与TRALI反应有关的PC含有显著高于对照PC的sCD 40 L水平。PMN在质膜上表达功能性CD 40，并且重组sCD 40 L（10 ng/mL-1 μ g/mL）快速（5分钟）引发PMN氧化酶。可溶性CD 40 L促进PMN介导的HMVECs细胞毒性，作为TRALI的2事件体外模型中的第二事件。我们的结论是，sCD 40 L，在血液成分储存过程中积累，有能力激活粘附的中性粒细胞，导致内皮损伤，并可能TRALI易感患者。
Transfusion-related acute lung injury (TRALI) is a form of posttransfusion acute pulmonary insufficiency that has been linked to the infusion of biologic response modifiers (BRMs), including antileukocyte antibodies and lipids. Soluble CD40 ligand (sCD40L) is a platelet-derived proinflammatory mediator that accumulates during platelet storage. We hypothesized that human polymorphonuclear leukocytes (PMNs) express CD40, CD40 ligation rapidly primes PMNs, and sCD40L induces PMN-mediated cytotoxicity of human pulmonary microvascular endothelial cells (HMVECs). Levels of sCD40L were measured in blood components and in platelet concentrates (PCs) implicated in TRALI or control PCs that did not elicit a transfusion reaction. All blood components contained higher levels of sCD40L than fresh plasma, with apheresis PCs evidencing the highest concentration of sCD40L followed by PCs from whole blood, whole blood, and packed red blood cells (PRBCs). PCs implicated in TRALI reactions contained significantly higher sCD40L levels than control PCs. PMNs express functional CD40 on the plasma membrane, and recombinant sCD40L (10 ng/mL-1 mu g/mL) rapidly (5 minutes) primed the PMN oxidase. Soluble CD40L promoted PMN-mediated cytotoxicity of HMVECs as the second event in a 2-event in vitro model of TRALI. We concluded that sCD40L, which accumulates during blood component storage, has the capacity to activate adherent PMNs, causing endothelial damage and possibly TRALI in predisposed patients.