SYNDECANS AND SYNDECAN INDUCERS IN THE RESPONSE TO LUNG INJURY

围产期肺部面临各种损伤的风险，这些损伤可能导致 慢性肺病，部分是因为防御不成熟，部分是因为 因为呼吸机的潜在有害影响 干预措施。 早产儿吸氧通气 肺部可能出现水肿、炎症和肺泡损伤 破坏。 这些反应可能导致纤维化和肺部异常 成长。 我们最近发现多配体家族的成员 细胞表面的硫酸乙酰肝素蛋白多糖是由 抗生素肽源自中性粒细胞，并且可以脱落到 受伤组织中的液体，包括气管抽吸物 通气婴儿。 该提议基于这样的假设： 肺对损伤的反应是由多种细胞介导的 效应器的作用可以通过与类肝素结合来改变 糖胺聚糖，并且可溶性多聚糖可以调节 这些效应器的动作。 我们将评估相关机制 多配体胞外域从细胞表面脱落并建立 可溶性多聚糖胞外域是否会改变 bFGF 的活性以及 HB-EGF、蛋白酶和抗蛋白酶以及趋化因子 IP-10 和 CATP 三． 我们将评估各种多糖的诱导活性 抗生素肽、纯化伤口液肽和重组 类似物试图澄清所涉及的分子和 诱导机制。 我们将分析肺部分泌物 通气婴儿的多配体和促进多配体的药物 脱落和多聚糖诱导。 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 调节细胞效应器活性的因素 参与对肺损伤的反应应该会导致新的预防措施 和治疗干预。

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.