CYTOKINES AND ADHESION MOLECULES IN HSV KERATITIS

HSV 角膜炎中的细胞因子和粘附分子

• 批准号: 2019903
• 负责人: ROBERT L HENDRICKS
• 金额: $ 18.53万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2019903
• 关键词: Langerhans' cell; cell adhesion molecules; cell migration; cellular pathology; corneal stroma; cytokine; disease /disorder model; enzyme linked immunosorbent assay; extracellular matrix; fluorescent dye /probe; genetic strain; herpes simplex virus 1; immunocytochemistry; inflammation; keratitis; laboratory mouse; monoclonal antibody; neutralizing antibody; ocular herpes; polymerase chain reaction; tissue /cell culture

DESCRIPTION: (Adapted from the applicant's abstract) Corneal inflammation is a significant cause of visual morbidity. Inflammation can be induced by a variety of infectious and noninfectious agents.The corneal stromal inflammation associated with HSV-1 infections is the leading infectious cause of blindness in this country. The KOS and RE strains of Herpes simplex virus (HSV-1) have been found to induce markedly different types of inflammation in the corneas of A/J mice.CD8 T lymphocytes play a critical role in the inflammation induced in the cornea by KOS HSV-1, which is characterized primarily by a mononuclear infiltrate. RE HSV-1 infection leads to a predominantly neutrophilic infiltration, in which CD4 T lymphocytes play an essential role. Since leukocyte extravasation and migration into inflammatory sites appear to be controlled by local expression of cytokines and adhesion molecules, the involvement of these molecules will be investigated in the corneal inflammation induced in mouse corneas by the KOS and RE strains of HSV-1. These studies will involve both in vivo and in vitro assays for leukocyte extravasation and migration. The cornea is an ideal tissue in which to conduct these studies becaused it is avascular.Thus, leukocytes that extravasate from the vessels at the peripheral margin of the cornea must migrate through several millimeters of tissue to reach the site of infection in the central cornea. This permits one to separately study the processes of extravasation and migration through the extracellular matrix of the corneal stroma. The involvement of various cytokines in the extravasion and migration of different populations of inflammatory cells into KOS- and RE HSV-1-infected corneas will be tested. This will be done in vivo by treatment of infected mice with monoclonal antibodies capable of neutralizing various cytokines, and then following the progress of the inflammatory response. The same antibodies will be employed that are need to block migration of leukocytes into infected corneal buttons, an assay recently developed in our laboratory. Similar studies will be conducted with antibodies to adhesion molecules and other inhibitors of the interaction of adhesion molecules with their ligands on vascular endothelium and extracellular matrix proteins.These studies may lead to the development of new means of intervening in the blinding inflammatory disease that is associated with HSV-1 corneal infections. These studies may also provide a useful paradigm for studying other inflammatory diesases that occur in the cornea as well as other tissues.

描述：（改编自申请人的摘要）角膜 炎症是视觉发病率的重要原因。 炎 可以由各种传染和非感染药物诱导。 与HSV-1感染相关的角膜基质炎症是 在这个国家，主要的失明感。 KOS和RE 疱疹病毒（HSV-1）的菌株已诱导 A/J小鼠的角膜中明显不同类型的炎症。CD8 T淋巴细胞在诱发的炎症中起关键作用 KOS HSV-1的角膜，主要由单核特征 浸润。 RE HSV-1感染导致主要嗜中性粒细胞 浸润，其中CD4 T淋巴细胞起着至关重要的作用。 自从 白细胞的渗出和迁移到炎症部位似乎 通过细胞因子和粘附分子的局部表达来控制， 这些分子的参与将在角膜中研究 KOS和RE菌株在小鼠角膜中诱导的炎症 HSV-1。 这些研究将涉及白细胞的体内和体外测定 奢侈和迁移。 角膜是理想的组织 进行这些研究是因为它是尸体的，因此，白细胞是 从角膜的外围边缘处的血管奢华必须 通过几毫米的组织迁移，到达 中央角膜中的感染。 这允许一个人单独学习 通过细胞外的溢出和迁移的过程 角膜基质的基质。 各种细胞因子参与 炎症种群的奢侈和迁移 将测试细胞进入KOS-和RE HSV-1感染角膜。 这会 通过用单克隆抗体处理感染的小鼠在体内完成 能够中和各种细胞因子，然后遵循 炎症反应的进展。 相同的抗体将是 需要阻止白细胞迁移到感染的 角膜按钮是最近在我们的实验室开发的一种测定法。 相似的 研究将使用抗粘附分子和其他的抗体进行 粘附分子与配体相互作用的抑制剂 在血管内皮和细胞外基质蛋白上。 可能导致发展新手段的介入 与HSV-1角膜感染有关的炎性疾病。 这些研究还可能为研究其他研究提供有用的范式 角膜以及其他组织中发生的炎性柴油酶。