Erythrocyte Transfusion in Acute Lung Injury During Sepsis

脓毒症期间急性肺损伤的红细胞输注

基本信息

批准号：
7406981
负责人：
Nilam S. Mangalmurti
金额：
$ 5.67万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7406981
关键词：
Acute Acute Lung Injury Adhesions Adult Respiratory Distress Syndrome Anemia Antioxidants Cell Adhesion Molecules Cells Clinical Critical Illness Daily Defense Mechanisms Development Disruption Endothelial Cells Epidemiologic Studies Equilibrium Erythrocyte Transfusion Erythrocytes Etiology Free Radicals Generations Goals Hemoglobin Homeostasis Host Defense Immune response In Vitro Inflammation Inflammatory Inflammatory Response Injury Intensive Care Units Ischemia Knockout Mice Knowledge Lead Leukocytes Lipids Lung Lung Inflammation Mediating Mediator of activation protein Membrane Modeling Morbidity - disease rate Mus NADPH Oxidase Neutrophil Activation Neutrophil Infiltration Oxidative Stress Oxygen Patients Personal Satisfaction Production Proteins Reactive Oxygen Species Sepsis Source Transfusion Vascular Permeabilities cell injury cytokine in vivo in vivo Model insight lung injury migration mortality mouse model neutrophil novel strategies oxidation septic

项目摘要

DESCRIPTION (provided by applicant): Red blood cell transfusions are routinely given to critically ill patients. Recent epidemiological studies have shown that red cell transfusions are associated with the development of lung injury, increased morbidity and mortality in the critically ill. The etiology underlying this association remains uncertain, as a clinical benefit has not been convincingly demonstrated with leukoreduction. The main premise of this study is that transfusion of the non-leukocyte component of red cell concentrates can pre-dispose the recipient to acute lung inflammation and injury during sepsis. We have developed an in vivo murine model whereby purified erythrocyte transfusion promotes neutrophilic accumulation in the lungs. The main goal of this proposal is to determine whether transfusion of purified erythrocytes during septic inflammation can lead to increased oxidative stress through the generation of reactive oxygen species (ROS), endothelial cell activation and lung injury. In Specific Aim 1 we will determine whether the non-leukocyte component of red cell concentrates can promote neutrophil mediated lung injury in a mouse model of sepsis. In Specific Aim 2, we will determine the impact of erythrocyte concentrates on endothelial cell activation, neutrophil-endothelial adhesion, and trans- endothelial migration in vitro. In Specific Aim 3, we will examine the effects of erythrocyte transfusions on the generation of reactive oxygen species ROS both in vitro and in our in vivo model using gp47 null mice deficient in NADPH oxidase activity. Knowledge derived from these studies may elucidate one mechanism underlying the consequences of red cell transfusion and provide new insight to a common problem in the critically ill.

描述（由申请人提供）：危重患者常规接受红细胞输注。最近的流行病学研究表明，红细胞输注与肺损伤的发生、危重病患者发病率和死亡率的增加有关。这种关联的病因学仍不确定，因为白细胞减少术的临床益处尚未得到令人信服的证明。这项研究的主要前提是，输注红细胞浓缩物中的非白细胞成分可以使受血者在败血症期间预先处理急性肺部炎症和损伤。我们开发了一种体内小鼠模型，纯化的红细胞输注可促进中性粒细胞在肺部积聚。该提案的主要目标是确定在化脓性炎症期间输注纯化红细胞是否会通过活性氧（ROS）的产生、内皮细胞活化和肺损伤而导致氧化应激增加。在具体目标 1 中，我们将确定红细胞浓缩物的非白细胞成分是否可以促进脓毒症小鼠模型中中性粒细胞介导的肺损伤。在具体目标 2 中，我们将确定红细胞浓缩物对体外内皮细胞活化、中性粒细胞-内皮粘附和跨内皮迁移的影响。在具体目标 3 中，我们将使用缺乏 NADPH 氧化酶活性的 gp47 null 小鼠，在体外和体内模型中检查红细胞输注对活性氧 ROS 生成的影响。从这些研究中获得的知识可能会阐明红细胞输注后果的一种机制，并为危重病人的常见问题提供新的见解。