Glycobiology of Inflammatory Lung Diseases

炎症性肺病的糖生物学

基本信息

批准号：
8289349
负责人：
RONALD L SCHNAAR
金额：
$ 220.75万
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 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8289349
关键词：
Affinity Allergic Animal Model Anti-Inflammatory Agents Anti-inflammatory Antibodies Apoptosis Arterial Fatty Streak Asthma Atherosclerosis Binding Binding Proteins CD22 antigen Carbohydrates Cardiovascular Diseases Carrier Proteins Cell surface Cells Cessation of life Chronic Obstructive Airway Disease Development Disease Disease model Environment Enzymes Epithelial Epithelial Cells Family Genes Glycobiology Goals Human Image In Vitro Individual Infiltration Inflammation Inflammation Mediators Inflammatory Inflammatory Response Inorganic Sulfates Knockout Mice Knowledge Lead Life 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 abstracting base design eosinophil experience human SIGLEC8 protein in vivo inhibitor/antagonist insight keratan sulfate Gal-6-sulfotransferase macrophage member mouse model nanoparticle neutrophil novel novel diagnostics programs receptor receptor expression sialic acid binding Ig-like lectin sialoadhesin skills 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（由申请人提供）：细胞表面聚糖和互补的聚糖结合蛋白与炎症过程密切相关。该计划团队的成员和其他人发现，Siglec家族的某些聚糖蛋白质家族的某些成员是炎症的抑制剂。这种肺部炎症性疾病的糖基疾病计划（LID-PEG）着重于Siglecs及其聚糖反感染者（配体）的抗炎功能，以调节肺部正在进行的炎症。主题：在肺组织上表达的特异性聚糖会在炎症细胞上接合互补的聚糖结合蛋白（SIGLEC-8，SIGLEC-9，SIGLEC-1），以限制肺部炎症。了解涉及的聚糖结构和聚糖结合蛋白的知识，对其表达的控制以及负责将聚糖互动转化为调节炎症反应的机制，将为炎症性肺部疾病的发展提供新的见解。靶向聚糖结合蛋白在炎症细胞上的合成聚糖纳米颗粒和抗体将限制炎症损伤。获得的见解可能会导致新颖的诊断工具和治疗性组成，这些工具和治疗与NHLBI目标相关的肺部炎症性疾病和其他组织的炎症性疾病。在三个主要的糖生物学中心的四个紧密整合的项目和两个核心将协调实现项目目标的努力：项目1，“通过瞄准Siglecs来治疗肺部炎症”（B. Bochner，Johns Hopkins）；项目2，“针对肺和心血管疾病的Siglec靶向纳米颗粒”（J. Paulson，Scripps）；项目3，“ SIGLEC-8和SIGLEC-9的人类肺反受体”（R. Schnaar，Johns Hopkins）；项目4，“ SIGLEC反受体的调节表达”（M. Tiemeyer，CCRC/U。Georgia）；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 Hopkins）。该计划得到了行政核心（核心A）和技能发展核心（核心B）的支持，该核心（核心B）为受训人员提供了三个中心的各种体验。该计划将为肺部炎症性疾病的糖基镜提供新的见解。相关性：哮喘和慢性阻塞性肺疾病（COPD），肺部疾病，引起广泛的疾病和死亡，涉及炎症细胞的浸润。通常，肺中的糖分子在炎症细胞上接合互补的糖结合分子，从而信号会停止并限制组织损伤。该项目定义了抗炎糖分子，并使用它们来开发新的治疗方法。（抽象的结尾）