Mouse model for sepsis

脓毒症小鼠模型

• 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
• 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

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）：