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: 3154394
• 负责人: GAIL S HABICHT
• 金额: $ 10.08万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 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 1986-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3154394
• 关键词: Lyme disease; arteritis; 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.

莱姆病是一种螺旋体病，由达米尼硬蜱叮咬传播 滴答声。 它的特点是一个环形皮肤病变，通常开始于 蜱附着部位，称为慢性游走性红斑（ECM）， 按发生频率递减顺序，由关节炎（通常是大关节）， 神经和心脏并发症。 致病关系 莱姆病螺旋体（LDS）感染与 皮肤损伤和关节炎的发展尚不清楚。 是 这些研究的目的是探索这些关系， 研究在兔子中产生的皮肤和关节损伤模型， 暴露于LDS。 在这样做更普遍的了解关节炎 由细菌感染引起的。 ECM将通过感染蜱的附着和皮内感染产生。 注射活动LDS。 此外，还将努力促使 用蜱唾液腺的蛋白质提取物治疗皮肤病变， 研究蜱因子在ECM发生中的作用。 LDS将是 物理和化学分离以产生外壳（OE）， 肽聚糖（PG）和脂多糖（LPS）成分。 这些 将测试部分引发皮肤损伤的能力。 的 OE包括整个LDS的大多数抗原决定簇，而LPS具有 有效的炎症和免疫调节作用。 PG来源于 当以小剂量给药时， 剂量 将对皮肤病变进行活检并进行组织学表征， 炎症细胞浸润的性质 其他病变将 用于水泡的人工诱导。 水泡里的液体 将分析是否存在炎症介质，包括 白三烯B4、组胺和白细胞介素1。 LDS及其组分也将在关节内注射， 用于诱发兔膝关节炎。 后多个时间 将检查膝关节是否有炎症迹象。 滑膜 将收集流体并相对于细胞 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、软骨和邻近骨中的关节炎病变 表征了