Mouse model for sepsis

脓毒症小鼠模型

基本信息

批准号：
7191582
负责人：
H Shaw Warren
金额：
$ 39.07万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-06-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7191582
关键词：
Affinity Agonist Alveolar Macrophages Ammonium Sulfate Animal Model Animals Bacteria Bacterial Toxins Biological Biological Assay Blood Bone Marrow Cattle Cavia Cell Adhesion Molecules Cell Line Cells Charge Chickens Communicable Diseases Complex Cultured Cells DNA Data Endothelial Cells Enzyme-Linked Immunosorbent Assay Equus caballus Family suidae Flagellin Future Goals Gram-Positive Bacteria Hamsters Hand Heating High Pressure Liquid Chromatography Human Hydrophobicity IRAK3 gene Immune response In Vitro Interleukin-6 Lead Lectin Lipopolysaccharides Lipoproteins Literature Lizards Lung MAPK14 gene Mass Spectrum Analysis Mediating Molecular Mus Oryctolagus cuniculus Pan Genus Pan troglodytes Papio Pattern Peptidoglycan Peripheral Blood Mononuclear Cell Peritoneal Peritoneal Macrophages Phosphotransferases Population Production Proteins Rattus Research Personnel Resistance Rodent STAT3 gene Sampling Sepsis Serum Signal Transduction Source Stimulus Sus scrofa System TLR2 gene TNF gene Techniques Technology Testing Time Tissues Toll-like receptors Toxin Umbilical vein Work base cell type cytokine design fetal human IRAK1 protein interest killings macrophage microbial monocyte mouse model pathogen peripheral blood programs protein purification research study resistance mechanism response size two-dimensional

项目摘要

DESCRIPTION (provided by applicant): Mice are one of the most commonly utilized species for the initial study of many infectious diseases, including the study of the host response to bacteria. However, mice are 100 to 100,000- fold more resistant than humans in most biological responses to the effects of bacterial lipopolysaccharide (LPS), and to many other microbial toxins. In the literature, and in our hands, macrophages from the two species are generally similar in their sensitivity to LPS, regardless of source. Our preliminary data indicate that there is a soluble substance in the serum of mice that strongly suppresses the production of IL-6 and TNF from mouse and human macrophages that are stimulated with many pathogen associated molecular pattern molecules (PAMPs). These data raise the possibility that the reason that mice are resistant to LPS and other bacterial toxins is the presence of this factor in their blood. The overall goal of the proposed work is to understand the mechanism(s) by which mice are resistant to LPS. Our first specific aim is to systematically study the sensitivity of macrophages and endothelial cells from different tissue compartments from mice and humans (where possible), as well as in cell lines, in the presence of serum from LPS-resistant animals (eg rodent, baboon) and LPS-sensitive animals (eg human, fetal calf). Our second specific aim is to purify the material from mouse serum that inhibits the production of TNF from mouse macrophages. Our third specific aim is to study the cellular level of signaling that is inhibited. The project has broad significance because most experiments using mouse cells are currently performed using media supplemented with fetal calf serum rather than mouse serum, because the proposed work will further our understanding of sepsis caused by bacterial pathogens, and because the work could eventually lead to better animal models for the study of sepsis.

描述（由申请人提供）：小鼠是许多传染病的初步研究中最常用的物种之一，包括研究宿主对细菌的反应。然而，在对细菌脂多糖 (LPS) 和许多其他微生物毒素的影响的大多数生物反应中，小鼠的抵抗力比人类高 100 至 100,000 倍。在文献和我们手中，这两个物种的巨噬细胞对 LPS 的敏感性通常相似，无论其来源如何。我们的初步数据表明，小鼠血清中存在一种可溶性物质，可以强烈抑制小鼠和人类巨噬细胞在许多病原体相关分子模式分子 (PAMP) 的刺激下产生 IL-6 和 TNF。这些数据表明，小鼠对脂多糖和其他细菌毒素具有抵抗力的原因可能是其血液中存在这种因子。拟议工作的总体目标是了解小鼠对脂多糖的抵抗机制。我们的第一个具体目标是系统地研究来自小鼠和人类（如果可能）的不同组织区室以及细胞系的巨噬细胞和内皮细胞在LPS抗性动物（例如啮齿动物、狒狒）血清存在下的敏感性）和LPS敏感动物（例如人类、胎牛）。我们的第二个具体目标是从小鼠血清中纯化出能够抑制小鼠巨噬细胞产生 TNF 的物质。我们的第三个具体目标是研究被抑制的信号传导的细胞水平。该项目具有广泛的意义，因为大多数使用小鼠细胞的实验目前都是使用补充有胎牛血清而不是小鼠血清的培养基进行的，因为拟议的工作将进一步我们对细菌病原体引起的脓毒症的理解，并且因为这项工作最终可能会带来更好的结果。用于研究败血症的动物模型。