CORE C - Infection and Inflammation Core

摘要 核心 C 设施支持针对项目特定目标的研究，包括规划和 执行实验性脓毒症队列研究、全血样本的血液学分析，以及 多种循环糖蛋白的测量，包括标记物的比较研究 脓毒症发作和进展期间的炎症过程。核心从而提供支持 解决该程序的中心假设，蛋白质糖基化和糖蛋白重塑改变了 凝血障碍和脓毒症炎症。 Core C 提供必要的实验和技术 功能包括分析来自小鼠和小鼠的实验和临床生物样本 人类物种，包括全血、血清、血浆，并根据要求提供尿液。与合作 项目，正如所发表的那样，核心开发了一种小鼠实验性脓毒症方案，其中包括 标准化和可重复的病原体感染和监测，并具有特定的数据包含阈值 代表小鼠脓毒症对五种不同人类细菌的反应的发生和进展 病原体和临床分离株。这种方法使得能够跨越特定目标的比较研究 这三个项目中的每一个都揭示了不同致病途径的存在，这些途径提供了一定程度的 由特定细菌病原体引起的脓毒症发病机制的分层。这些研究将进一步 如本申请的研究项目中所示进行扩展。此外，核心设施也将竣工 对小鼠血液样本以及人类志愿者和败血症患者的血液进行血液学分析 包括白细胞和红细胞的测量、血细胞比容值、血红蛋白丰度和多个 血小板指标。根据要求进行的其他分析将包括细胞丰度的流式细胞术研究 代表各种血细胞谱系，包括 T 和 B 淋巴细胞、中性粒细胞、单核细胞、嗜酸性粒细胞、 和嗜碱性粒细胞。这些血液学分析将提供给现场当地项目研究人员，并将 使用相同的设备进行标准化，用于在实验室进行可比较的血液学分析 项目研究的第二个地点。核心设施还将从血清中生成多重分析物数据集， 在健康和败血症的情况下，来自小鼠和人类的血浆或尿液样本。这些复用 实验使用研究者选择的和可定制的测定来产生定量测量 重要的细胞因子、生长因子以及其他各种生理学生物指标 系统，特别是那些影响炎症过程的系统。超过一千种蛋白质可以 在不同组的分析物中进行选择性测量，并且其中许多蛋白质的丰度较低，并且 无法使用质谱法进行常规检测和准确测量。核心从而提供了 意味着查询难以量化的较低丰度蛋白质。核心C将提升速率 计划研究的进展并促进拟议研究之间的研究整合和协同作用。

SUMMARY The Core C facility supports research addressing the specific aims of the projects to include the planning and execution of experimental sepsis cohort studies, hematological analyses of whole blood samples, and measurements of multiple circulating glycoproteins that includes comparative studies of markers of inflammatory processes during the onset and progression of sepsis. The Core thereby provides support addressing the central hypothesis of the program, Protein glycosylation and glycoprotein remodeling alter the coagulopathy and inflammation of sepsis. Core C provides essential experimental and technological capabilities that include the analysis of experimental and clinical biological samples derived from mouse and human species including whole blood, serum, plasma, and, when requested, urine. In collaboration with the projects, and as published, the core has developed an experimental sepsis protocol in the mouse that includes standardized and reproducible pathogen infection and monitoring with specific thresholds for data inclusion representing the onset and progression of mouse sepsis in response to five different human bacterial pathogens and clinical isolates. This approach has enabled comparative studies spanning the specific aims of each of the three projects while revealing the presence of different pathogenic pathways that provide a degree of stratification in the pathogenesis of sepsis due to specific bacterial pathogens. These studies will be further expanded as indicated in the research projects of this application. In addition, the core facility will complete hematology analyses of mouse blood samples as well as blood from human volunteers and sepsis patients to include measurements of white and red blood cells, hematocrit values, hemoglobin abundance, and multiple platelet metrics. Additional analyses when requested will include flow cytometric studies of cell abundance representing various blood cell lineages including T and B lymphocytes, neutrophils, monocytes, eosinophils, and basophils. These hematology analyses will be provided to onsite local project researchers and will be standardized with identical equipment that is used to undertake comparable hematology analyses at the second site of project research. The core facility will also generate multiplex analyte datasets from serum, plasma, or urine samples from mouse and human species in the context of health and sepsis. These multiplex experiments use investigator-selected and customizable assays yielding quantitative measurements of essential and important cytokines, growth factors, and various other biological indicators of physiological systems especially those that impinge upon inflammatory processes. Over a thousand proteins can be selectively measured in various sets of analytes, and many of these proteins are found at low abundance and cannot be routinely detected and accurately measured using mass spectrometry. The core thereby provides a means to query lower abundance proteins that are difficult to quantify otherwise. Core C will enhance the rate of progress of program research and facilitate research integration and synergies among the studies proposed.