Glycobiology of Inflammatory Lung Diseases

描述(申请人提供)：细胞表面多聚糖和互补的多聚糖结合蛋白与炎症过程密切相关。这个项目团队的成员和其他人发现，Siglec糖蛋白结合蛋白家族的某些成员是炎症的抑制物。这项肺炎性疾病卓越糖科学计划(LID-PEG)专注于Siglecs及其糖链拮抗剂受体(配体)在缓解肺部持续炎症中的抗炎功能。主题：肺组织表达的特定糖链与炎症细胞上的互补糖链结合蛋白(Siglec-8、Siglec-9、Siglec-1)结合，以限制肺部炎症。了解涉及的糖链结构和糖链结合蛋白，它们的表达控制，以及负责将糖链参与转化为炎症反应调节的机制，将为炎症性肺部疾病的进展提供新的见解。以炎症细胞上的多糖结合蛋白为靶点的人工合成的葡聚糖修饰的纳米颗粒和抗体将限制炎症损害。所获得的见解可能导致新的诊断工具和治疗组合物，用于治疗与NHLBI目标相关的肺部和其他组织的炎症性疾病。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Siglec治疗肺部炎症”(B.Bochner，Johns Hopkins)；项目2，“针对肺部和心血管疾病的Siglec靶向纳米颗粒”(J.Paulson，斯克里普斯)；项目3，“人肺Siglec-8和Siglec-9的反受体”(R.Schna，Johns Hopkins)；项目4，“Siglec反受体的调节表达”(M.Timeyer，CCRC/U。核心C，“共享资源核心：碳水化合物合成”(J.Paulson，斯克里普斯)；核心D，“炎症性动物模型核心”(Z.朱，约翰霍普金斯)。该方案由一个行政核心(核心A)和一个技能发展核心(核心B)提供支持，为受训人员提供在三个中心的不同经验。该计划将为肺部炎症性疾病的血糖科学提供新的见解。相关性：哮喘和慢性阻塞性肺疾病(COPD)是导致广泛疾病和死亡的肺部疾病，涉及破坏性炎症细胞的渗透。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，发出信号阻止它们，限制组织损伤。该项目定义了抗炎糖分子，并用它们来开发新的治疗方法。(摘要结束)

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)