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: 3157446
• 负责人: GAIL S HABICHT
• 金额: $ 9.1万
• 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 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3157446
• 关键词: Lyme disease; arthritis; bacterial disease; disease vectors; erythema; heart disorder; inflammation; joint disorder; leukotrienes; lipopolysaccharides; medical complication; peptidoglycan; skin disorder; spirochetes disease

Lyme disease is a spirochetosis transmitted by the bite of Ixodes dammini 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 diseases spirochete (LDS) and the development of skin lesions and arthritis are not yet understood. It is the purpose of these studies to explore those relationships by investigating model skin and joint lesions produced in the rabbit by exposure to the LDS. In so doing a more general understanding of arthritis produced by bacterial infection should result. ECM will be produced by attachment of infected ticks and by intradermal injection of motile LDS. In addition, an attempt will be made to induce a skin lesion with a proteinaceous extract of tick salivary glands in order to study the role of tick factors in the development of ECM. LDS will be physically and chemically fractionated to yield the outer envelope (OE), peptidoglycan (PG) and lipopolysaccharide (LPS) constituents. These moieties will be tested for their ability to initiate a skin lesion. The OE includes most of the antigenic determinants of whole LDS while LPS has potent inflammatory and immunoregulatory effects. The PG derived from other bacterial species have systemic toxicity when administered in small doses. Skin lesions will be biopsied and characterized histologically with respect to the nature of the inflammatory cell infiltrate. Other lesions will be used for the artificial induction of blisters. Fluid from the blisters will be analyzed for the presence of inflammatory mediators including leukotriene B4, histamine and interleukin 1. LDS and their fractions will also be injected intraarticularly in the rabbit knee for the induction of arthritis. At various times after exposure the knees will be examined for signs of inflammation. Synovial fluid will be harvested and characterized with respect to the cellular content as well as for the presence of inflammatory mediators including leukotriene B4, interleukin 1, histamine, prostaglandin E2 and collagenase. Animals will be sacrificed and the histopathology of the arthritic lesions in the synovium, cartilage and adjacent bone characterized.

莱姆病是一种由达米尼硬蜱叮咬传播的螺旋体病 滴答声。 它的特点是环形皮肤病变，通常开始于 蜱附着部位，称为慢性游走性红斑 (ECM)， 按频率递减顺序，通常是大关节的关节炎， 神经和心脏并发症。 致病关系 莱姆病螺旋体 (LDS) 感染与 皮肤损伤和关节炎的发展尚不清楚。 这是 这些研究的目的是通过以下方式探索这些关系 研究用兔子制作的皮肤和关节损伤模型 接触摩门教徒。 这样做对关节炎有更全面的了解 应由细菌感染产生。 ECM 将通过感染蜱的附着和皮内注射产生 注射运动LDS。 此外，还将尝试诱导 用蜱唾液腺的蛋白质提取物来治疗皮肤病变 研究蜱因子在 ECM 发展中的作用。 LDS 将是 物理和化学分馏以产生外膜（OE）， 肽聚糖（PG）和脂多糖（LPS）成分。 这些 将测试各部分引发皮肤损伤的能力。 这 OE 包含整个 LDS 的大部分抗原决定簇，而 LPS 则包含 有效的炎症和免疫调节作用。 PG 源自 其他细菌种类在少量施用时具有全身毒性 剂量。 皮肤病变将进行活检并进行组织学表征 与炎症细胞浸润的性质有关。 其他病变将会 用于人工诱导水泡。 水泡中流出液体 将分析炎症介质的存在，包括 白三烯B4、组胺和白细胞介素1。 LDS 及其组分也将被注射到关节内 兔膝用于诱发关节炎。 之后的不同时间 暴露膝盖将检查是否有炎症迹象。 滑膜 将收集液体并根据细胞特征进行表征 含量以及炎症介质的存在，包括 白三烯 B4、白细胞介素 1、组胺、前列腺素 E2 和 胶原酶。 将处死动物并进行组织病理学检查 滑膜、软骨和邻近骨的关节炎病变 特点。