Mechanisms of Salivary and Lacrimal Inflammation

描述：血液中自身反应性和效应性淋巴细胞的迁移 进入唾液腺和泪腺是一个关键事件在启蒙和 干燥S综合征患者腺体炎症和损伤的维持。这 迁移涉及顺序淋巴细胞/内皮细胞的多步骤级联 黏附和激活事件。目标是识别淋巴细胞和 内皮细胞黏附分子、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 淋巴细胞中的这些分子迁移到这些组织中。非肥胖型糖尿病 (NOD)小鼠，一个具有良好特征的人类干燥S综合征的模型，将被 用于这些研究。 特定目标1将定义黏附分子、趋化因子、 NOD小鼠发炎的唾液和泪腺中的趋化因子受体。 这些黏附分子和趋化因子(及其受体)在血管内皮细胞生长中的作用 淋巴细胞向炎症腺体的迁移将在功能研究中进行评估 在特定目标2中。特定目标3将确定是否治疗NOD小鼠 针对AIMS 1中定义的黏附分子或趋化因子的抗体 2能预防发展中的唾液和泪腺炎症。

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.