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: 6410560
• 负责人: MERTON R BERNFIELD
• 金额: $ 20.88万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6410560
• 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，部分原因是如果不成熟的防御，部分原因是， 由于呼吸机的潜在有害影响， 干预措施。 早产儿辅助供氧通气 可以获得表现出水肿，炎症和肺泡 杀伤性 这些反应可导致纤维化和肺异常 增长 我们最近发现， 细胞表面硫酸乙酰肝素蛋白聚糖，我们被诱导的一个 来自中性粒细胞的抗生素肽，并且可以脱落到 受伤组织中的液体，包括 通风的婴儿 这一建议是基于这样的假设， 肺对损伤的反应由多种细胞介导， 其作用可通过与肝素样结合而改变的效应物 糖胺聚糖，并且可溶性多配体聚糖可以调节 这些效应器的作用。 我们将评估 多配体蛋白聚糖胞外域从细胞表面脱落， 可溶性多配体蛋白聚糖胞外域是否改变bFGF的活性， HB-EGF、蛋白酶和抗蛋白酶以及趋化因子IP-10和CATP 三. 我们将评估多配体蛋白聚糖的诱导活性， 抗菌肽，净化伤口液肽和重组 类似物，试图澄清所涉及的分子和 诱导机制。 我们将分析 用于多配体聚糖和促进多配体聚糖的试剂的通气婴儿 脱落和多配体蛋白聚糖诱导。 这些结果将与 临床和结果数据，以深入了解 多配体在围产期肺损伤反应中的作用 阐明 调节细胞效应物活性的因子 参与肺损伤的反应应该导致新的预防性 和治疗干预。