Leukocyte trafficking in thoracic grafts

胸廓移植物中的白细胞贩运

• 批准号: 8921741
• 负责人: Daniel Kreisel
• 金额: --
• 依托单位: ST. LOUIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-10-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8921741
• 关键词: Adaptor Signaling Protein; Adhesions; Allografting; Area; Cardiac; Chest; Complex; Cues; Development; Endothelial Cells; Endothelium; Goals; Heart; Heart Transplantation; Heart failure; Human; Image; Immune; Immunologic Receptors; Inflammation; Inflammatory; Integrins; Investigation; Ischemia; Knowledge; Laboratories; Lead; Leukocyte Trafficking; Leukocytes; Mediating; Mediator of activation protein; Methods; Microscopy; Modeling; Molecular; Mus; Myocardial; Myocardial Ischemia; Myocardial tissue; Neutrophil Infiltration; Organ; Organ Preservation; Outcome; Pathway interactions; Phenotype; Population; Procedures; Process; Production; Reperfusion Injury; Reperfusion Therapy; Role; Secondary to; Signal Transduction; Site; Staging; Sterility; Structure of left gastric vein; TLR4 gene; TYROBP gene; Techniques; Testing; Therapeutic Intervention; Time; Tissue Grafts; Tissues; Transplantation; Vascular Endothelial Cell; Veterans; Work; adaptive immunity; chemokine; clinically significant; effective therapy; implantation; improved; in vivo; innovation; intravital imaging; isoimmunity; macrophage; migration; neutrophil; novel; novel therapeutic intervention; novel therapeutics; public health relevance; research study; success; trafficking; treatment strategy; two-photon

 DESCRIPTION (provided by applicant): Myocardial ischemia reperfusion injury, a consequence of organ preservation and implantation, adversely impacts both early and late outcomes after heart transplantation. As heart failure is highly prevalent among the veteran population, this area of investigation is of very high significance. While neutrophils are critical mediators of myocardial ischemia reperfusion injury, little is known about their trafficking and activation requirements during this form of sterile inflammation. Utilizing our newly developed technique of intravital imaging of beating mouse hearts, we have uncovered a role for innate immune molecules in donor hearts for entry of neutrophils into the graft tissue of freshly reperfused cardiac transplants. This application proposes to study mechanisms for neutrophil recruitment during myocardial ischemia reperfusion injury of heart grafts and will allow for the development of new therapeutic strategies.

 描述（由申请人提供）： 心肌缺血再灌注损伤是器官保存和移植的结果，对心脏移植后的早期和晚期结局都有不利影响。由于心力衰竭在退伍军人群体中非常普遍，因此该领域的调查具有非常高的意义。虽然中性粒细胞是心肌缺血再灌注损伤的关键介质，但对这种无菌炎症形式中的中性粒细胞运输和活化要求知之甚少。利用我们新开发的跳动小鼠心脏活体成像技术，我们发现了供体心脏中先天免疫分子在中性粒细胞进入新鲜再灌注心脏移植物组织中的作用。本申请旨在研究心脏移植物心肌缺血再灌注损伤过程中中性粒细胞募集的机制，并将有助于开发新的治疗策略。