CORE C - Infection and Inflammation Core

摘要 核心C设施支持涉及项目具体目标的研究，以包括规划和 进行实验性败血症队列研究，全血样本血液学分析，以及 多种循环糖蛋白的测定，包括对多种循环糖蛋白标志物的比较研究 脓毒症发生和发展过程中的炎症过程。因此，核心提供支持 针对该计划的中心假设，蛋白质糖基化和糖蛋白重塑改变了 脓毒症的凝血障碍和炎症。核心C提供基本的实验和技术 能力，包括分析实验和临床生物样本从小鼠和 人类物种，包括全血、血清、血浆，如果需要，还包括尿液。与 项目，正如发表的那样，核心已经在小鼠身上开发了一种实验性的脓毒症方案，包括 标准化和可重复的病原体感染和监测，具有特定的数据纳入阈值 代表五种不同人类细菌对小鼠脓毒症的发生和发展 病原体和临床分离株。这种方法使比较研究能够跨越以下具体目标 这三个项目中的每一个都揭示了不同致病途径的存在，提供了一种程度 由特定的细菌病原体引起的脓毒症的发病机制中的分层。这些研究将进一步 如本申请的研究项目所示进行了扩展。此外，核心设施将完成 小鼠血液样本以及人类志愿者和脓毒症患者血液的血液学分析 包括测量白血球和红血球、红细胞压积、血红蛋白丰度和 血小板指标。如有要求，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， 以及嗜碱性粒细胞。这些血液学分析将提供给现场的当地项目研究人员，并将 标准化使用相同的设备，用于进行可比的血液学分析 项目研究的第二个地点。核心设施还将从血清中生成多个分析物数据集， 血浆，或来自健康和败血症背景下的人类和小鼠的尿样。这些多路电视 实验使用研究人员选择的可定制的分析方法，可产生以下定量测量 必要和重要的细胞因子、生长因子和其他各种生理指标 系统，尤其是那些影响炎症过程的系统。一千多种蛋白质可以 在各种分析物中选择性地测量，这些蛋白质中的许多都是低丰度和低丰度 不能用质谱仪进行常规检测和准确测量。由此，该核心提供了 以其他方式难以量化的低丰度蛋白质的查询手段。核心C将提高 评估方案研究的进展情况，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.