IMMUNOPATHOLOGY IN THE EYES WITH EXPERIMENTAL UVEITIS

实验性葡萄膜炎眼部的免疫病理学

• 批准号: 3841222
• 负责人: C-C CHAN
• 金额: --
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3841222
• 关键词: antiinflammatory agents; autoimmune disorder; cellular immunity; disease /disorder model; eye pharmacology; helper T lymphocyte; histochemistry /cytochemistry; immunomodulators; immunopathology; immunopharmacology; in situ hybridization; inflammation; laboratory mouse; laboratory rat; leukocyte activation /transformation; retinal pigment epithelium; uveitis

The identity and topographic localization of immunocompetent cells and the alteration of surface markers on ocular resident cells in mice and rodents with experimental autoimmune uveoretinitis (EAU) were analyzed by immunohistochemical studies and in situ hybridization. T lymphocytes were the predominantly infiltrating cells in rat EAU, yet both macrophages and T helpers/inducers were the predominantly infiltrating cells in mouse EAU. The migration of inflammatory cells from vessels into target sites is directed by adhesion molecules that can be expressed on vascular endothelium and other resident cells in the eye. T-lymphocyte specificity is directed to small fragments of antigen bound to cell surface major histocompatibility complex (MHC) molecules, which are presented on the surface of specialized antigen-presenting cells. The expression of MHC class II antigens was observed on ocular resident cells such as retinal pigment epithelium (RPE), retinal vascular endothelium, keratocytes, fibroblasts, and ciliary epithelium in rodents. The expression of MHC class II antigens is confined to ocular resident cells immediately at the inflammatory sites in mouse EAU, which is characterized by focal lesions and chronicity. Both the infiltrating cell subpopulation and the expression of class II antigens on ocular resident cells can be altered by various immunomodulating agents. Experimental endotoxin-induced uveitis (EIU) is a model for anterior uveitis in humans. The mechanism of this inflammation is still unclear, although activation of phospholipase A2 (PLA2) may play a role in the initiation and propagation of this disease. The particular vascular structure of the anterior uvea and the role of adhesion molecules (such as intercellular adhesion molecule and endothelial leukocyte adhesion molecule) and their ligand (lymphocyte function-associated antigen) also were examined in EIU and EAU models. Inhibition of PLA2 (chlorpromazine, antiflammin, etc.) and adhesion molecules can abrogate EIU.

免疫活性细胞的身份和拓扑定位， 小鼠眼常驻细胞表面标志物的改变， 患有实验性自身免疫性葡萄膜视网膜炎（EAU）的啮齿动物， 通过免疫组织化学研究和原位杂交分析。 T淋巴细胞是大鼠EAU的主要浸润细胞， 但巨噬细胞和T辅助/诱导细胞是主要的 小鼠EAU中的浸润细胞。 炎症细胞的迁移 由粘附分子引导从血管进入靶部位， 可以在血管内皮细胞和其他驻留细胞上表达， the eye. T淋巴细胞特异性针对小片段的 与细胞表面主要组织相容性复合体结合的抗原 分子，这些分子呈现在专门的 抗原呈递细胞 MHC Ⅱ类抗原的表达 在视网膜色素等眼驻留细胞上观察到 上皮（RPE），视网膜血管内皮，角膜细胞， 成纤维细胞和睫状上皮。 MHC的表达 II类抗原仅限于眼常驻细胞， 小鼠EAU中的炎症部位，其特征在于局灶性 病变和慢性化。 浸润细胞亚群和 II类抗原在眼驻留细胞上的表达可以 被各种免疫调节剂改变。 实验性内毒素诱导的葡萄膜炎（EIU）是前葡萄膜炎的模型。 人类的葡萄膜炎 这种炎症的机制仍然是 尽管磷脂酶A2（PLA 2）的激活可能在 在这种疾病的发生和传播中起着重要作用。 的特定 前葡萄膜血管结构及其在粘连中的作用 分子（如细胞间粘附分子和内皮细胞粘附分子） 白细胞粘附分子）及其配体（淋巴细胞 EIU和EAU中也检测到功能相关抗原 模型 抑制PLA 2（氯丙嗪、抗炎素等）和 粘附分子可以消除EIU。