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LYME DISEASE--DEVELOPMENT OF SKIN LESIONS AND ARTHRITIS

莱姆病——皮肤损伤和关节炎的发展

基本信息

批准号：
2079118
负责人：
GAIL S HABICHT
金额：
$ 12.94万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-23 至 1995-02-28
项目状态：
已结题

项目摘要

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.

莱姆病是由感染螺旋体疏螺旋体引起的通过硬蜱的叮咬传播的伯格多费氏病。它是以环状皮肤损害为特征，通常始于扁虱附着，称为慢性红斑迁徙(ECM)，在频率递减，通常由大关节的关节炎引起，神经和心脏并发症。致病关系在感染莱姆病螺旋体和发展为皮肤、心脏、大脑和关节的损伤才刚刚开始明白了。尽管这种疾病有许多症状，可能会成为在莱姆病患者中发现慢性极少数螺旋体。这个认为这种疾病的发病机制是由生物因素引起的假说放大少数生物体的影响通过释放高活性螺旋体产品或从生产组织损伤的内源性介质，或两者兼而有之，将被调查。在……里面目前对伯氏杆菌致病成分的研究将是检查过了。通过这样做，对细菌有了更全面的了解致病机制，尤其是细菌诱导的关节炎。细菌脂多糖(LPS)和多糖肽(PG) 墙已被证明可以调节组织损伤。伯氏杆菌的内毒素和PG 将被提取出来，并根据其理化、免疫学和生物学特性。糖和脂多糖的脂类部分和氨基酸将被鉴定。 PG的组成。培养的和新鲜分离的内毒素将对螺旋体进行比较。针对内毒素和PG的抗体将是用来中和这些分子的生物活性。将使用抗内毒素的单抗来鉴定表位负责内毒素的炎症行为，并定位内毒素用免疫金标记法和电子显微镜观察。炎症性病变注射PG或LPS后在动物皮肤中产生的以形态和内源诱导为特征的炎症的中介物。莱姆关节炎的大鼠模型将是探讨内毒素和前列腺素在关节形成中的作用。