Leukocyte trafficking in thoracic grafts

胸廓移植物中的白细胞贩运

• 批准号: 9206084
• 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/9206084
• 关键词: Adaptor Signaling Protein; Adhesions; Allografting; Area; Cardiac; Chest; Complex; Cues; Development; Endothelial Cells; Endothelium; Fresh Tissue; Goals; Heart; Heart Injuries; Heart Transplantation; Heart failure; Human; Image; Immune; Immune signaling; 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; Sterility; Structure of left gastric vein; TLR4 gene; TYROBP gene; Techniques; Testing; Therapeutic Intervention; Time; Tissue Grafts; Tissues; Transplantation; Vascular Endothelial Cell; Veterans; adaptive immune response; chemokine; clinically significant; effective therapy; experimental study; implantation; improved; in vivo; innovation; intravital imaging; isoimmunity; macrophage; migration; neutrophil; novel; novel therapeutic intervention; novel therapeutics; public health relevance; receptor; 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.