Mechanisms of Salivary and Lacrimal Inflammation

唾液和泪道炎症的机制

• 批准号: 6420997
• 负责人: SARA A MICHIE
• 金额: $ 26.53万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6420997
• 关键词: B lymphocyte; NOD mouse; Sjogren's syndrome; T lymphocyte; cell migration; chemokine; cytokine receptors; disease /disorder model; flow cytometry; fluorescence microscopy; gene expression; gene targeting; genetically modified animals; immunocytochemistry; immunofluorescence technique; immunotherapy; inflammation; lacrimal apparatus; laser capture microdissection; leukocyte activation /transformation; monoclonal antibody; polymerase chain reaction; protein structure function; receptor expression; salivary glands; vascular cell adhesion molecule; vascular endothelium

DESCRIPTION: The migration of autoreactive and effector lymphocytes from blood into salivary and lacrimal glands is a key event in the initiation and maintenance of glandular inflammation and damage in Sjogren?s syndrome. This migration involves a multi-step cascade with sequential lymphocyte/endothelial adhesion and activation events. The goals are to identify lymphocyte and endothelial adhesion molecules, chemokines, and chemokine receptors that are expressed in inflamed salivary and lacrimal glands, and to define the roles of these molecules in lymphocyte migration to these tissues. Non-obese diabetic (NOD) mice, a well-characterized model for human Sjogren?s syndrome, will be used for these studies. Specific Aim 1 will define the expression of adhesion molecules, chemokines, and chemokine receptors in inflamed salivary and lacrimal glands from NOD mice. The roles of these adhesion molecules and chemokines (and their receptors) in lymphocyte migration to inflamed glands will be assessed in functional studies in Specific Aim 2. Specific Aim 3 will determine if treatment of NOD mice with antibodies directed against adhesion molecules or chemokines defined in Aims 1 and 2 will prevent the development of salivary and lacrimal gland inflammation.

描述：血液中自身反应性淋巴细胞和效应淋巴细胞的迁移 进入唾液腺和泪腺是启动的关键事件， 维持干燥综合征的腺体炎症和损伤？s综合征。这 迁移涉及一个多步骤级联，依次是淋巴细胞/内皮细胞 粘附和活化事件。目的是鉴定淋巴细胞， 内皮粘附分子、趋化因子和趋化因子受体， 在发炎的唾液腺和泪腺中表达，并确定 这些分子参与淋巴细胞向这些组织的迁移。非肥胖糖尿病 (NOD)小鼠，一个良好的表征模型，为人类干燥？s综合征，将是 用于这些研究。 具体目标1将定义粘附分子，趋化因子， 以及NOD小鼠发炎的唾液腺和泪腺中的趋化因子受体。 这些粘附分子和趋化因子（及其受体）在 在功能研究中评估淋巴细胞向发炎腺体的迁移 具体目标2。具体目标3将确定是否用以下药物治疗NOD小鼠 针对目的1中定义的粘附分子或趋化因子的抗体 和2将防止唾液腺和泪腺炎症的发展。