UPTAKE OF IG BY VAGINAL EPITHELIAL CELLS

阴道上皮细胞对 IG 的摄取

• 批准号: 6654008
• 负责人: Deborah J Anderson
• 金额: $ 18.05万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6654008
• 关键词: Chlamydiaceae; antibacterial agents; antibody receptor; antiviral agents; biological transport; cell adhesion molecules; cervix; clinical research; cytokine; epithelium; herpes simplex virus 2; human immunodeficiency virus 1; human tissue; immunocytochemistry; immunoglobulin A; immunoglobulin G; menstrual cycle; monoclonal antibody; mucosal immunity; receptor expression; sexually transmitted diseases; tissue /cell culture; vagina

This project addresses the mechanism, regulation and functional significance of immunoglobulin (Ig) uptake buy human vaginal and cervical epithelial cells, and the potential use of this mechanism to enhance the efficacy of topically administered vaginal microbicides containing antibodies for the prevention of STDs. Specific Aim 1 focuses on the mechanism of IgG and monomeric IgA uptake by vaginal and cervical epithelial cells. Tissue explants and polarized/stratified epithelial cell cultures will be used to determine: 1) whether Ig uptake is directional, 2) the intracellular localization of Ig, 3) Ig retention kinetics, and 4) Ig cervical epithelial cells. Immunohistochemical studies will determine whether Ig receptor expression and uptake of IgG or mIgA in vivo is related to hormonal changes during the menstrual cycle or to inflammatory conditions. Parallel studies will be conducted in vitro at protein and mRNA levels using hormone and cytokine treated epithelial cell lines. Specific Aim 3 will address the physiological relevance of intracellular Ig. Epithelial cells will be treated with human monoclonal antibodies/plantibodies that have neutralizing activity against pathogens that infect epithelial cells in vitro (HSV-2, chlamydia and HIV-1), or bind to human leukocyte antigens (ICAM1, SPA1); subsequent Ig-treated and untreated cells will be challenged with the respective pathogen(s) in cell- free (HSV-2, chlamydia, HIV-1) or cell-associated (HIV-1) form and inter- and intracellular antibody-mediated protection will be monitored. This project will also provide immortalized cell lines and human genital tract issues for the performance of other studies in the Topic Microbicide Program Project.

该项目解决了免疫球蛋白（IG）摄取的机制，调控和功能意义，购买人类阴道和宫颈上皮细胞，以及该机制的潜在使用来增强含有局部施用的含有阴道微生物的抗体的疗效，以预防STDS。具体目标1的重点是阴道和宫颈上皮细胞的IgG和单体IgA摄取的机理。组织外植体和极化/分层的上皮细胞培养物将用于确定：1）Ig摄取是否为方向，2）Ig的细胞内定位，3）Ig保留动力学和4）Ig宫颈上皮细胞。免疫组织化学研究将确定Ig受体表达和体内IgG或Miga的摄取是否与月经周期期间的激素变化有关还是与炎症条件有关。平行研究将在蛋白质和mRNA水平上使用激素和细胞因子处理的上皮细胞系进行体外研究。具体目标3将解决细胞内IG的生理相关性。上皮细胞将用人类的单克隆抗体/植物体治疗，这些抗体/植物体具有中和活性，该病原体在体外感染上皮细胞（HSV-2，衣原体和HIV-1），或与人类白细胞抗原（ICAM1，SPA1，SPA1）结合；随后的IG处理和未处理的细胞将在无细胞（HSV-2，衣原体，HIV-1）或细胞相关（HIV-1）形式以及细胞内和细胞内抗体介导的保护中受到各自的病原体的挑战。该项目还将提供永生的细胞系和人类生殖道问题，以在主题Microbicide计划项目中进行其他研究。