Properties of stored RBCs: minimization of immune and vascular reactivity

储存红细胞的特性：免疫和血管反应性最小化

• 批准号: 8304319
• 负责人: Philip J. Norris
• 金额: $ 53.52万
• 依托单位: VITALANT
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-18 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8304319
• 关键词: Acute; Address; Adverse effects; Affect; Age; Allogenic; Anti-Inflammatory Agents; Anti-inflammatory; Biological; Blood; Blood Platelets; Blood Transfusion; Blood Vessels; Blood Volume; Brain; Cardiac Surgery procedures; Cell Adhesion; Cell Communication; Cell surface; Cells; Cerebrum; Clinical; Clinical Research; Clinical Trials; Coagulants; Critical Illness; Dependence; Disease Outcome; Endothelial Cells; Erythrocyte Transfusion; Erythrocytes; Event; Exposure to; Frequencies; Genetic Predisposition to Disease; Hemorrhage; Human; Immune; Immune response; Immune system; Immunology; Immunosuppression; Immunosuppressive Agents; In Vitro; Incidence; Inflammation; Inflammation Mediators; Inflammatory; Interleukin-17; Intervention; Knowledge; Lead; Length; Lesion; Leukocytes; Life; Link; Liquid substance; Measurement; Measures; Membrane; Methods; Natural Killer Cells; Operative Surgical Procedures; Outcome; Participant; Patients; Peripheral Blood Mononuclear Cell; Permeability; Play; Policies; Property; Randomized; Randomized Clinical Trials; Regulatory T-Lymphocyte; Research; Research Personnel; Research Proposals; Resuscitation; Risk Factors; Role; Solutions; Suspension substance; Suspensions; System; T-Lymphocyte; T-Lymphocyte Subsets; Technology; Testing; Transfusion; Vascular Endothelial Cell; Vascular System; blood product; carbohydrate receptor; chemokine; cytokine; immunoregulation; improved; in vivo; inflammatory marker; injured; insight; mortality; neutrophil; novel; pathogen; patient population; prevent; response

Project Summary Blood transfusion is a life-saving intervention for subjects with acute blood loss or hematological disturbance, and approximately 5 million people per year receive red blood cell transfusions annually in the US. While blood transfusions clearly help those in need, the immune and inflammatory side-effects of transfusions may have detrimental consequences in transfusion recipients. Recent clinical studies suggest that older RBC units may be associated with worsened outcome in some patient populations. The purpose of this research proposal is to discover changes that occur in stored RBC units and test methods of reversing or preventing these changes. The thrust of the research will be to define how RBC units affect innate and adaptive immune responses and vascular reactivity in transfusion recipients and how storage of RBC units can alter these transfusion effects. In addition to detailed in vitro studies, the proposal will explore these same parameters in participants of a clinical trial correlating age of blood with clinical outcome in critically ill transfusion recipients. The broad hypothesis behind this proposal is that storage of RBCs increases their ability to modulate immune responses and to activate vascular endothelial cells in transfusion recipients. Leukoreduced RBC units will be characterized throughout storage for the ability to modulate innate and adaptive immune responses. RBC- endothelial cell interaction will be measured using cutting-edge flow cell technology to measure the frequency and strength of RBC adhesion to endothelial cells and to measure the activation of endothelial cells exposed to fresh and stored RBC units. After defining the changes in the immunomodulatory and vasoactivating properties of stored RBCs, methods of preventing these changes will be explored. Sophisticated immunology measurements will be made after RBC exposure, including multiplex measurement of cytokine/chemokine induction in T cells and neutrophils, induction of proliferative responses, and skewing of regulatory and IL-17 secreting T cell subsets. To test the in vivo relevance of the study findings, the immune parameters measured will be extended to subjects receiving RBC units stored for short vs. long periods in a randomized clinical trial, and relevant immune parameters will be correlated with disease outcome (e.g. is immune suppression linked with infectious complications?). This research proposal joins a team of investigators with complementary expertise to significantly advance our knowledge of potentially harmful immunomodulatory and vasoactivating effects of transfusion and their dependence on storage of RBCs. Importantly, the proposal will validate the knowledge gained and systems developed in a human clinical trial and will evaluate methods of preventing harmful effects of RBC storage using in vitro systems.

项目摘要 输血是对急性失血或血液系统紊乱患者的救命干预措施， 在美国，每年大约有500万人接受红细胞输注。而当 输血显然对有需要的人有帮助，但输血的免疫和炎症副作用可能 对输血接受者造成有害后果。最近的临床研究表明，较老的红细胞单位 可能与某些患者群体的预后恶化有关。这项研究的目的是 建议发现存储的红细胞单位中发生的变化，并测试逆转或预防的方法 这些变化。这项研究的主旨将是确定红细胞单位如何影响先天免疫和获得性免疫 输血受者的反应和血管反应性以及红细胞单位的储存如何改变这些 输血效果。除了详细的体外研究外，该提案还将在 一项临床试验的参与者将血液年龄与危重输血接受者的临床结果相关联。 这一提议背后的广泛假设是，红细胞的储存增加了它们调节免疫的能力 并激活输血受者的血管内皮细胞。白细胞减少的红细胞单位将是 在整个存储过程中具有调节先天和适应性免疫反应的能力。RBC- 将使用尖端流动细胞技术测量内皮细胞相互作用的频率 和RBC与内皮细胞的黏附强度，并测量暴露于 新鲜和储存的RBC单位。在明确了免疫调节和血管激活的变化后 存储的红细胞的属性，将探索防止这些变化的方法。尖端免疫学 红细胞暴露后将进行测量，包括细胞因子/趋化因子的多重测量 T细胞和中性粒细胞的诱导，增殖反应的诱导，以及调节因子和IL-17的偏斜 分泌T细胞亚群。为了检验研究结果的体内相关性，测量了免疫参数 将扩展到在随机临床试验中接受短期与长期储存的RBC单位的受试者， 相关的免疫参数将与疾病结果相关(例如，免疫抑制与 有感染性并发症？) 这项研究提案加入了一个拥有互补专业知识的调查团队，以显著推动我们的 对输血可能有害的免疫调节和血管激活作用及其影响的认识 对红细胞储存的依赖。重要的是，该提案将验证所获得的知识和系统 在人体临床试验中开发，并将评估预防红细胞储存有害影响的方法 使用体外系统。

项目成果

Microparticle profile and procoagulant activity of fresh-frozen plasma is affected by whole blood leukoreduction rather than 24-hour room temperature hold.

• DOI: 10.1111/trf.12602
• 发表时间: 2014-08
• 期刊: Transfusion
• 影响因子: 2.9
• 作者: Chan KS;Sparrow RL
• 通讯作者: Sparrow RL

In vitro measures of membrane changes reveal differences between red blood cells stored in saline-adenine-glucose-mannitol and AS-1 additive solutions: a paired study.

膜变化的体外测量揭示了储存在盐水-腺嘌呤-葡萄糖-甘露醇和 AS-1 添加剂溶液中的红细胞之间的差异：一项配对研究。

• DOI: 10.1111/trf.12344
• 发表时间: 2014
• 期刊: Transfusion
• 影响因子: 2.9
• 作者: Sparrow,RosemaryL;Sran,Amrita;Healey,Geraldine;Veale,MargaretF;Norris,PhilipJ
• 通讯作者: Norris,PhilipJ

Microparticle content of plasma for transfusion is influenced by the whole blood hold conditions: pre-analytical considerations for proteomic investigations.

• DOI: 10.1016/j.jprot.2012.07.013
• 发表时间: 2012-12-05
• 期刊: Journal of proteomics
• 影响因子: 3.3
• 作者: Sparrow RL;Chan KS
• 通讯作者: Chan KS

Properties of stored red blood cells: understanding immune and vascular reactivity.

• DOI: 10.1111/j.1537-2995.2011.03103.x
• 发表时间: 2011-04
• 期刊: Transfusion
• 影响因子: 2.9
• 作者: Spinella PC;Sparrow RL;Hess JR;Norris PJ
• 通讯作者: Norris PJ

Stored red blood cell susceptibility to in vitro transfusion-associated stress conditions is higher after longer storage and increased by storage in saline-adenine-glucose-mannitol compared to AS-1.

• DOI: 10.1111/trf.13138
• 发表时间: 2015-09
• 期刊: Transfusion
• 影响因子: 2.9
• 作者: Mittag D;Sran A;Chan KS;Boland MP;Bandala-Sanchez E;Huet O;Xu W;Sparrow RL
• 通讯作者: Sparrow RL