REGULATION OF CHEMOKINE RECEPTOR EXPRESSION DURING SEPSIS

脓毒症期间趋化因子受体表达的调节

• 批准号: 8167223
• 负责人: BARBARA SHERRY
• 金额: $ 2.53万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167223
• 关键词: Cells; Clinical; Computer Retrieval of Information on Scientific Projects Database; Data; Defect; Funding; Goals; Grant; In Vitro; Infection; Institution; Left; Link; Lung; Outcome; Patients; Predisposition; Protocols documentation; Regulation; Research; Research Personnel; Resources; Secondary to; Sepsis; Signal Transduction; Source; Surface; Therapeutic Intervention; United States National Institutes of Health; adverse outcome; base; beta-Chemokines; chemokine receptor; improved; macrophage; receptor expression; response; septic

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our long-range goal is to overcome mechanisms that subvert effective pulmonary defense in septic patients, thereby improving clinical outcome. The objective of this protocol is to assess whether beta chemokine receptor expression is suppressed in circulating macrophages isolated from septic patients, and if so, to evaluate whether the magnitude of this defect correlates with (1) the type of infection (e.g. gram-negative versus gram-positive)or (2) with increased susceptibility to secondary lung infection. The central hypothesis, formulated on the basis of strong in vitro data, is that in septic patients the systemic release of bacterial products, including lipopolysaccahride, triggers a sustained loss of a class of beta chemokine receptors from the surface of macrophages, leaving these cells essentially anergic to beta chemokine signals. The rationale that underlies the proposed research is that the identification of a link between dysregulated beta chemokine receptor responses and adverse outcomes in septic patients would provide us with a previously unrecognized target for therapeutic intervention.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们的长期目标是克服脓毒症患者中破坏有效肺防御的机制，从而改善临床结果。 本方案的目的是评估从脓毒症患者中分离的循环巨噬细胞中β趋化因子受体表达是否受到抑制，如果是，则评估该缺陷的程度是否与（1）感染类型（例如革兰氏阴性vs.革兰氏阳性）或（2）继发性肺部感染易感性增加相关。 基于强有力的体外数据制定的中心假设是，在脓毒症患者中，细菌产物（包括脂多糖）的全身释放引发了巨噬细胞表面一类β趋化因子受体的持续丧失，使这些细胞基本上对β趋化因子信号无反应性。 提出的研究的基本原理是，确定败血症患者中β趋化因子受体反应失调和不良结局之间的联系，将为我们提供一个以前未被认识的治疗干预靶点。