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: 6110694
• 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: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6110694
• 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.

围产期肺部有各种损伤的危险，这些损伤可能导致