REGULATION OF CHEMOKINE RECEPTOR EXPRESSION DURING SEPSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们的长期目标是克服破坏败血症患者有效肺防御的机制，从而改善临床结果。该方案的目的是评估从脓毒症患者分离的循环巨噬细胞中β-趋化因子受体的表达是否受到抑制，如果是的话，评估这种缺陷的程度是否与(1)感染类型(例如，革兰氏阴性与革兰氏阳性)或(2)继发肺部感染的易感性增加有关。建立在强大的体外数据基础上的中心假说是，在脓毒症患者体内，包括脂多糖在内的细菌产物的系统性释放，触发了巨噬细胞表面一类β-趋化因子受体的持续丢失，使这些细胞基本上对β-趋化因子信号失去能力。这项拟议研究的基本原理是，确定脓毒症患者异常调节的β-趋化因子受体反应与不良结局之间的联系将为我们提供一个以前未被认识到的治疗干预靶点。

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.