SYNDECANS AND SYNDECAN INDUCERS IN THE RESPONSE TO LUNG INJURY

SYNDECAN 和 SYNDECAN 诱导剂对肺损伤的反应

• 批准号: 6273188
• 负责人: MERTON R BERNFIELD
• 金额: $ 20.42万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273188
• 关键词: animal tissue; bronchopulmonary dysplasia; clinical research; human subject; hyperoxia; laboratory mouse; laboratory rat; low birth weight infant human; molecular pathology; perinatal; syndecan

The perinatal lung is at risk for a variety of injuries that can lead to chronic lung disease, in part because if immature defenses, and in part, because of the potentially deleterious effects of ventilator interventions. Premature infants ventilated with supplemental oxygen can acquire injured lungs that exhibit edema, inflammation, and alveolar destruction. These responses can lead to fibrosis and abnormal lung growth. We have recently found that members of the syndecan family of cell surface heparan sulfate proteoglycans we be induced by an antibiotic peptide derived from neutrophils, and can be shed into the fluids in injured tissues, including the tracheal aspirates of ventilated infants. This proposal is based on the hypothesis that the response of the lung to injury is mediated by a variety of cellular effectors whose action can be modified by binding to heparin-like glycosaminoglycans, and that the soluble syndecans can regulate the actions of these effectors. We will evaluate the mechanisms by which the syndecan ectodomains are shed from the cell surface and establish whether the soluble syndecan ectodomains modify the activity of bFGF and HB-EGF, proteases and antiproteases, and the chemokines IP-10 and CATP III. We will assess the syndecan inductive activity of various antibiotic peptides, of purifies wound fluid peptides and recombonant analogs in an attempt of clarify the molecules involved and the mechanism of induction. We will analyze pulmonary secretions of ventilated infants for syndecans and for agents that promote syndecan shedding and syndecan induction. These results will be correlated with clinical and outcome data to gain an insight into the role of the syndecans in the response of the perinatal lung to injury. Elucidating the factors that regulate the activity of the cellular effectors involved in the response to lung injury should lead to novel preventive and therapeutic interventions.

围产期肺有各种损伤的风险，这些损伤可能导致 慢性肺部疾病，部分原因是如果防御不成熟，部分原因是， 因为呼吸机的潜在有害影响 干预措施。补充氧气的早产儿 可获得表现为浮肿、炎症和肺泡的受损肺 毁灭。这些反应会导致纤维化和肺部异常。 成长。我们最近发现Syndecan家族的成员 细胞表面硫酸乙酰肝素蛋白多糖的诱导 来自中性粒细胞的抗菌肽，可以被释放到 损伤组织中的液体，包括沙门氏菌的气管吸出物 呼吸正常的婴儿。这一建议是基于这样的假设： 肺对损伤的反应是由多种细胞因子介导的 其作用可通过与类肝素结合来修改的效应器 糖胺多聚糖，而可溶性的合十聚糖可以调节 这些效应器的动作。我们将评估通过哪些机制 Syndecan胞外结构域从细胞表面脱落并建立 可溶性Syndecan胞外结构域是否影响bFGFs的活性 HB-EGF、蛋白和抗蛋白水解酶以及趋化因子IP-10和CATP III.我们将评估不同类型的Syndecan诱导活性 抗菌多肽，净化伤口液多肽和重组体 类比，试图阐明所涉及的分子和 归纳的机制。我们将分析肺部分泌物 使用通气机的婴儿服用辛迪康和促进辛迪康的制剂 脱胶和整形诱导法。这些结果将与 临床和结局数据，以深入了解 合并素在围产期肺损伤反应中的作用澄清 调节细胞效应器活性的因素 参与对肺损伤的反应应导致新的预防措施 和治疗性干预。