DEVELOPMENTAL EXPRESSION OF CHEMOKINES & THEIR RECEPTORS

趋化因子的发育表达

• 批准号: 6486249
• 负责人: DARLENE A CALHOUN
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-13 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6486249
• 关键词: age difference; bacterial disease; bone marrow; chemokine; chemotaxis; clinical research; cord blood; cytokine receptors; developmental genetics; developmental immunology; embryo /fetus; embryo /fetus cell /tissue; gene expression; genetic regulation; human pregnant subject; immunocytochemistry; liver; messenger RNA; neonatal intensive care; neutrophil; newborn human (0-6 weeks); nucleic acid quantitation /detection; premature infant human; serology /serodiagnosis; tissue /cell preparation

DESCRIPTION: (provided by applicant) Despite the development of newer and more effective antibiotic therapies, sepsis related mortality in neonates undergoing intensive care has remained constant for nearly two decades. The rate of infection among these neonates ranges from 25% to 50%, with bacterial infection remaining a major cause of death and long-term morbidity. The cost of caring for premature neonates, who are the most susceptible to infection, represents over 50% of the total dollars expended for neonatal intensive care unit (NICU) services. The unique susceptibility of the human neonate to serious and overwhelming bacterial infections relates in part to deficiencies of antibody, complement, and T lymphocytes. However, while deficiencies in these contribute to the neonate s susceptibility, neutrophil defects appear to be the major host defense abnormality. Functional defects in neonatal polymorphonuclear leukocyte adherence, aggregation, chemotaxis, phagocytosis, and intracellular killing have been described in both the term and preterm infant. Of these defects, neutrophil chemotaxis, as assessed by in vitro assays, is abnormal at birth. While term infants rapidly establish normal chemotactic function, the process of postnatal maturation begins two to three weeks after birth in the preterm infant and proceeds very slowly. Neutrophils follow a concentration gradient of chemotactic factors in their movement from the vascular compartment to the site of microbial invasion. Chemokines are chemotactic cytokines that largely control leukocyte migration. While considerable information has emerged in the past ten years related to the role of chemokines in the adult, very little information exists as to the physiologic significance of chemokines in the neonate. Candidate chemokine/chemokine receptors for influencing neutrophil chemotaxis include members of the CXC chemokines. We propose that understanding the gene regulation for the expression of specific chemokine receptors (CXCR) during development would enhance our understanding of chemotaxis in the neonate. We further propose that defining circulating concentrations of chemokines critical for neutrophil migration would be essential to understanding their role in both health and disease.

描述：（由申请人提供）尽管开发了更新和 更有效的抗生素治疗，新生儿败血症相关死亡率 接受重症监护的患者近二十年来一直保持不变。的 这些新生儿的感染率从25%到50%不等， 感染仍然是死亡和长期发病的主要原因。成本 照顾早产儿，他们最容易受到感染， 占新生儿重症监护费用总额的50%以上 新生儿重症监护室（NICU）服务。人类新生儿对 严重和压倒性的细菌感染部分与缺乏 抗体，补体和T淋巴细胞然而，尽管存在缺陷， 这些都有助于新生儿的易感性，中性粒细胞缺陷似乎 是主要的宿主防御异常新生儿功能缺陷 多形性白细胞粘附、聚集、趋化性、吞噬作用， 在足月和早产儿中， 婴儿。在这些缺陷中，中性粒细胞趋化性，如通过体外 检测显示，出生时异常。足月儿很快就能建立正常的 趋化功能，出生后成熟的过程开始两到三个 早产儿在出生后数周内发生，进展非常缓慢。中性粒 遵循趋化因子的浓度梯度， 微生物入侵部位的血管区室。趋化因子是 趋化性细胞因子在很大程度上控制白细胞迁移。而 在过去的十年里，出现了大量与这一角色有关的信息。 在成年人的趋化因子，很少有信息存在， 新生儿趋化因子的生理意义。候选 影响嗜中性粒细胞趋化性的趋化因子/趋化因子受体包括 CXC趋化因子的成员。我们认为， 调节特定趋化因子受体（CXCR）的表达， 发展将提高我们对新生儿趋化性的理解。我们 进一步提出定义趋化因子的循环浓度 对中性粒细胞迁移至关重要，这对于了解它们的 在健康和疾病中的作用。