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Glycobiology of Inflammatory Lung Diseases

炎症性肺病的糖生物学

基本信息

批准号：
9277536
负责人：
RONALD L SCHNAAR
金额：
$ 223.62万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9277536
关键词：
Affinity Allergic Animal Model Anti-Inflammatory Agents Anti-inflammatory Antibodies Apoptosis Arterial Fatty Streak Asthma Atherosclerosis Binding Binding Proteins Cadaver Carbohydrates Cardiovascular Diseases Carrier Proteins Cell surface Cells Cessation of life Chronic Obstructive Airway Disease Disease model Enzymes Epithelial Epithelial Cells Family Genes Glycobiology Goals Human Image In Vitro Individual Infiltration Inflammation Inflammation Mediators Inflammatory Inflammatory Response Knockout Mice Knowledge Lead Ligands Lipids Liposomes Lung Lung Inflammation Lung diseases Mus National Heart, Lung, and Blood Institute Nose Polysaccharides Principal Investigator Process Regulation Resource Sharing Signal Transduction Structure Structure of parenchyma of lung Testing Therapeutic Tissues Translating Unspecified or Sulfate Ion Sulfates Vascular Endothelial Cell base design eosinophil experience humanized mouse in vivo inflammatory lung disease inflammatory milieu inhibitor/antagonist insight macrophage member mouse model nanoparticle neutrophil novel novel diagnostics programs receptor receptor expression sialic acid binding Ig-like lectin sialoadhesin skill acquisition sugar tool

项目摘要

DESCRIPTION (provided by applicant): Cell surface glycans and complementary glycan binding proteins are intimately involved in inflammatory processes. Members of this Program team and others discovered that certain members of the siglec family of glycan binding proteins are inhibitors of inflammation. This Lung Inflammatory Disease Program of Excellence in Glycosciences (LID-PEG) focuses on the anti-inflammatory functions of siglecs and their glycan counter-receptors (ligands) in moderating ongoing inflammation in the lung. THEME: Specific glycans expressed on lung tissues engage complementary glycan binding proteins (Siglec-8, Siglec-9, Siglec-1) on inflammatory cells to limit lung inflammation. Knowledge of the glycan structures and glycan binding proteins involved, the control of their expression, and the mechanisms responsible for translating glycan engagement into regulation of the inflammatory response will provide new insights into the progression of inflammatory lung diseases. Synthetic glycan-decorated nanoparticles and antibodies that target glycan binding proteins on inflammatory cells will limit inflammatory damage. The insights gained may lead to novel diagnostic tools and therapeutic compositions that treat inflammatory diseases of the lung and other tissues relevant to the goals of the NHLBI. Four closely integrated Projects and two Cores at three major glycobiology centers will coordinate efforts to reach the Project goals: Project 1, "Treating lung inflammation by targeting siglecs" (B. Bochner, Johns Hopkins); Project 2, "Siglec-targeted nanoparticles for lung and cardiovascular disease" (J. Paulson, Scripps); Project 3, "Human lung counter-receptors for Siglec-8 and Siglec-9" (R. Schnaar, Johns Hopkins); Project 4, "Regulated expression of siglec counter-receptors" (M. Tiemeyer, CCRC/U. Georgia); Core C, "Shared Resources Core: Carbohydrate Synthesis" (J. Paulson, Scripps); and Core D, "Inflammatory Animal Models Core" (Z. Zhu, Johns Hopkins). The Program is supported by an Administrative Core (Core A) and a Skills Development Core (Core B) that provides trainees with diverse experiences at the three centers. This Program will provide novel insights into the glycosciences of lung inflammatory diseases. RELEVANCE: Asthma and Chronic Obstructive Pulmonary Disease (COPD), lung diseases that cause extensive illness and death, involve infiltration of damaging inflammatory cells. Normally, sugar molecules in the lung engage complementary sugar binding molecules on inflammatory cells, signaling them to halt and limiting tissue damage. This project defines anti-inflammatory sugar molecules and uses them to develop new treatments. (End of Abstract)

描述（由申请方提供）：细胞表面聚糖和互补聚糖结合蛋白密切参与炎症过程。该计划团队的成员和其他人发现，聚糖结合蛋白的siglec家族的某些成员是炎症抑制剂。这个糖科学卓越的肺部炎症性疾病计划（LID-PEG）专注于siglecs及其聚糖反受体（配体）在调节肺部持续炎症中的抗炎功能。主题：肺组织上表达的特异性聚糖与炎性细胞上的互补聚糖结合蛋白（Siglec-8、Siglec-9、Siglec-1）结合，以限制肺部炎症。了解所涉及的聚糖结构和聚糖结合蛋白，其表达的控制，以及负责将聚糖参与转化为炎症反应调节的机制，将为炎症性肺病的进展提供新的见解。合成聚糖修饰的纳米颗粒和靶向炎症细胞上聚糖结合蛋白的抗体将限制炎症损伤。所获得的见解可能导致新的诊断工具和治疗组合物，治疗与NHLBI目标相关的肺部和其他组织的炎性疾病。四个紧密结合的项目和三个主要糖生物学中心的两个核心将协调努力，以实现项目目标：项目1，“通过靶向单克隆抗体治疗肺部炎症”（B。Bochner，Johns霍普金斯）;项目2，“Siglec-靶向纳米颗粒用于肺和心血管疾病”（J. Paulson，Scripps）;项目3，“Siglec-8和Siglec-9的人肺反受体”（R. Schnaar，Johns霍普金斯）;项目4，“调节的siglec反受体表达”（M. Tiemeyer，CCRC/U。格鲁吉亚）;核心C，“共享资源核心：碳水化合物合成”（J. Paulson，Scripps）;和核心D，“炎症动物模型核心”（Z. Zhu，Johns霍普金斯）。该方案得到行政核心（核心A）和技能发展核心（核心B）的支持，为学员提供三个中心的各种经验。该计划将为肺部炎症性疾病的糖科学提供新的见解。相关性：哮喘和慢性阻塞性肺疾病（COPD），导致广泛疾病和死亡的肺部疾病，涉及破坏性炎症细胞的浸润。正常情况下，肺中的糖分子与炎症细胞上的互补糖结合分子结合，向它们发出信号以停止和限制组织损伤。该项目定义了抗炎糖分子，并利用它们开发新的治疗方法。(End摘要）