Animal and Human Sample Repository Core

动物和人类样本库核心

• 批准号: 8643335
• 负责人: CHRISTOPHER P O'DONNELL
• 金额: $ 25.19万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-03 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8643335
• 关键词: Acute Lung Injury; Adult Respiratory Distress Syndrome; Affect; Alveolar; Animal Model; Animals; Autopsy; Bacteria; Biochemical; Biological; Biology; Blood Gas Analysis; Body Fluids; Cannulas; Cardiolipins; Cells; Cessation of life; Chronic; Collaborations; Collection; Conscious; Critical Illness; Development; Diet; Disease; Enteral; Evans blue stain; Exposure to; Extravasation; Fatty acid glycerol esters; Gases; Glucose; Goals; Harvest; Human; Human Resources; Hyperglycemia; Hyperoxia; Hypoxia; Image; Immune system; Implant; In Vitro; Inflammatory; Infusion procedures; Institutional Review Boards; Interstitial Lung Diseases; Intervention; Intravenous; Leadership; Ligation; Liquid substance; Lung; Measurement; Mechanics; Mediator of activation protein; Medical; Modeling; Molecular; Mus; Myelogenous; Nutrient; Organelles; Outcome Assessment; Oxygen Consumption; Pathogenesis; Pathway interactions; Patients; Pattern; Permeability; Phenotype; Physiological; Pneumonia; Presbyterian Church; Production; Proteins; Puncture procedure; Registries; Research; Research Personnel; Risk; Role; Sampling; Sepsis; Services; Signal Pathway; Signal Transduction; Specimen; Stomach; Structure of parenchyma of lung; Suppressor-Effector T-Lymphocytes; Therapeutic Intervention; Tissue Banking; Tissue Banks; Tissue Sample; Tissues; Toxin; Translating; Transplantation; University Hospitals; Vasomotor; Work; alveolar epithelium; animal model development; animal resource; cell type; cohort; design; human disease; human tissue; in vivo; intraperitoneal; lung injury; novel; pathogen; pneumocyte; preclinical study; programs; repository; respiratory; small molecule; subcutaneous; vascular inflammation

The acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury (All) affects 100- 200K people in the U.S. yearly leading to death in nearly 35% of patients. ARDS is characterized by neutrophilic inflammation, vascular leak, and alveolar filling with proteinaceous fluid. This Program Project Proposal (P01) focuses on elucidating the role of cardiolipin (CL) as a novel damage associated molecular pattern (DAMP-CL) and mediator of tissue damage in acute lung injury. The alveolar epithelium and innate immune system are central to the development of ARDS. The three primary projects detailed within the P01 focus on expounding cardiolipin biology in these key cell types; type II alveolar pneumocytes in Projects 1 and 2 and inflammatory cells including the recently characterized myeloid derived suppressor cell in Project 3. Core C (Animal Models and Human Sample Repository) is designed to optimize the translational exploration of the mechanisms identified in vitro in Projects 1-3 whereby cardiolipin leads to progressive cellular and subsequently tissue damage in All. The Core will serve to standardize the characterization of murine models of acute lung injury across the various projects using bacterial pathogens or hyperoxic insult as indicated. Core personnel will perform physiologic measurements for project investigators including Flexivent lung mechanics and permeability assessments along with tissue and fluid collection for dissemination to project investigators. In addition, a key component of the Core services will be to provide de-identified human tissue and fluid samples (collected via an ongoing IRB approved registry and biospecimen repository and existing Divisional tissue banks) to project investigators for verification of human relevance of novel findings from the bench or from murine models. In providing these services, Core C integrates tightly and interacts closely with all projects comprising the P01 proposal.

急性呼吸窘迫综合征（ARDS）是急性肺损伤（ALL）中最严重的一种， 在美国，每年有20万人死亡，导致近35%的患者死亡。急性呼吸窘迫综合征的特征是嗜酸性炎症、血管渗漏和肺泡充满蛋白质样液体。本项目建议书（P01）的重点是阐明心磷脂（CL）作为一种新型损伤相关分子模式（DAMP-CL）和急性肺损伤组织损伤介质的作用。肺泡上皮细胞和先天性免疫系统在ARDS的发生发展中起着重要作用。P01中详细描述的三个主要项目重点阐述了这些关键细胞类型中的心磷脂生物学;项目1和2中的II型肺泡肺细胞和项目2中的炎性细胞，包括最近表征的髓源性抑制细胞。 3.核心C（动物模型和人类样本库）旨在优化项目1 - 3中体外确定的机制的翻译探索，其中心磷脂导致所有患者进行性细胞和随后的组织损伤。核心将用于标准化使用细菌病原体或高氧损伤的各种项目中急性肺损伤小鼠模型的表征。核心人员将为项目研究者进行生理测量，包括通气肺力学和渗透性评估，以及沿着组织和液体收集，以分发给项目研究者。此外，核心服务的一个关键组成部分将是向项目研究者提供去识别的人体组织和体液样本（通过正在进行的IRB批准的登记和生物标本储存库以及现有的部门组织库收集），以验证实验室或鼠模型中新发现的人体相关性。在提供这些服务时，Core C与P01提案中的所有项目紧密集成并密切互动。