LYME DISEASE--DEVELOPMENT OF SKIN LESIONS AND ARTHRITIS

莱姆病——皮肤损伤和关节炎的发展

• 批准号: 3157450
• 负责人: GAIL S HABICHT
• 金额: $ 12.74万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-23 至 1994-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3157450
• 关键词: Borrelia; Lyme disease; arthritis; bacterial cytopathogenic effect; bacterial proteins; carbohydrate sequence; carbohydrates; disease /disorder model; electron microscopy; high performance liquid chromatography; inflammation; laboratory mouse; laboratory rabbit; laboratory rat; lipopolysaccharides; monoclonal antibody; peptidoglycan; protein sequence; skin disorder

Lyme disease is caused by infection with a spirochete, Borrelia burgdorferi which is transmitted by the bite of Ixodes ticks. It is characterized by an annular skin lesion, usually starting at the site of tick attachment, known as erythema chronicum migrans (ECM) and, in decreasing order of frequency, by arthritis usually of the large joints, neurological and cardiac complications. The pathogenic relationships between infection with the Lyme disease spirochete and the development of lesions in the skin, heart, brain and joints are just beginning to be understood. Although the disease has many symptoms and may become chronic, very few spirochetes are found in Lyme disease patients. The hypothesis that the pathogenesis of this disease results from biological amplification of the effects of small numbers of organisms through the release of highly active spirochetal products or from the production of endogenous mediators of tissue injury, or both, will be investigated. In the present studies pathogenic components of B. burgdorferi will be examined. In so doing a more general understanding of bacterial pathogenesis and especially of bacteria-induced arthritis should result. Bacterial lipopolysaccharides (LPS) and peptidoglycans (PG) from the cell wall have been shown to mediate tissue damage. B. burgdorferi LPS and PG will be extracted and characterized with respect to their physicochemical, immunological and biological properties. Sugar and lipid moieties of the LPS will be identified as will the amino acid composition of the PG. LPS from cultured and freshly isolated spirochetes will be compared. Antibodies specific for LPS and PG will be used to neutralize the biological activities of these molecules. Monoclonal anti-LPS antibodies will be used to identify the epitopes responsible for the inflammatory actions of LPS and to locate the LPS using immunogold labeling and electron microscopy. Inflammatory lesions produced in animal skins following injection of PG or LPS will be characterized with respect to morphology and induction of endogenous mediators of inflammation. A rat model of Lyme arthritis will be investigated for the roles of LPS and PG in arthritogenesis.

莱姆病是由一种螺旋体--疏螺旋体感染引起的 通过硬蜱叮咬传播的伯氏螺旋体病。 是 以环状皮肤损伤为特征，通常始于 蜱附着，称为慢性游走性红斑（ECM）， 频率降序，关节炎通常是大关节， 神经和心脏并发症。 致病关系 莱姆病螺旋体感染与 皮肤、心脏、大脑和关节的病变才刚刚开始 明白 虽然这种疾病有许多症状，并可能成为 在莱姆病患者中很少发现慢性螺旋体。 的 这种疾病的发病机制是由生物学 放大少数生物体的影响， 高活性螺旋体产物的释放或 将研究组织损伤的内源性介质或两者。 在 目前对B的致病成分进行了研究。伯格多费里将是 考察 通过这样做，我们可以更全面地了解细菌 发病机制，特别是细菌引起的关节炎。 来自细胞的细菌脂多糖（LPS）和肽聚糖（PG） 已经显示壁介导组织损伤。 B。伯氏菌LPS和PG 将被提取和表征， 理化、免疫学和生物学特性。 糖和 LPS的脂质部分将被鉴定为氨基酸 来自培养的和新鲜分离的PG.LPS的组成 将比较螺旋体。 LPS和PG的特异性抗体将被 用于中和这些分子的生物活性。 将使用单克隆抗LPS抗体鉴定表位 负责LPS的炎症作用并定位LPS 用免疫金标记和电子显微镜。 炎性病变 在注射PG或LPS后动物皮肤中产生的 其特征在于形态学和内源性诱导 炎症介质。 莱姆关节炎的大鼠模型将 研究LPS和PG在关节炎发生中的作用。