TARGETING OF ADCC IN PERIODONTAL DISEASE

本申请的目标是建立微生物- 靶向抗体依赖性细胞介导的细胞毒性 作为慢性牙周炎的致病因素 疾病 初步数据显示， 制剂能够符合几种类型的标准 靶细胞，包括人淋巴母细胞系，鸡 和绵羊红细胞以及人牙龈成纤维细胞。 一旦 这些细菌被结合，针对它们的抗体能够 将ADCC效应细胞引导至靶标，从而产生ADCC效应细胞。 破坏哺乳动物细胞。 我们建议ADCC“ “靶向”发生在牙周炎中并导致组织破坏。 因此，特征性牙龈微生物群落在任何阶段， 牙周病发展以及植物群结合 对ADCC的表达有着深远的影响 以及随后的组织损伤。 我们建议：1）研究 靶向ADCC中的重要因子，包括效应细胞 亚群、溶解机制和细菌的影响 ADCC效应子功能的制剂;和2）检查 牙周病状态与ADCC的关系 通过检查健康受试者和患者血清中的活性 抗体亲和力、免疫球蛋白亚类和ELISA作用 滴度 该模型的特征将提供背景 需要将其确定为发展中的病因因素， 牙周病，并将提供进一步的动力， 临床评价，最终目标是 药理学控制的机制。

The goal of this application is to establish a model of microbial- targeted antibody-dependent cell-mediated cytotoxicity (ADCC) as an etiologic factor in chronic inflammatory periodontal disease. Preliminary data indicates that a variety of bacterial preparations are capable of adhering to several types of standard target cells, including human lymphoblastoid cell lines, chicken and sheep erythrocytes, and human gingival fibroblasts. Once these bacteria are bound, antibodies to them are capable of directing the ADCC effector cells to the target, resulting the destruction of the mammalian cell. We propose that ADCC " targeting" occurs in periodontitis and results in tissue destruction. Thus, the characteristic gingival microflora at any stage in the development of periodontal disease, and that flora's ability to bind to tissues, will have a profound effect on the expression of ADCC and subsequent tissue damage. We propose to: 1) study the factors important in targeted ADCC, including effector cell subpopulations, lytic mechanisms, and the influence of bacterial preparations in ADCC effector function; and 2) examine the relationship between periodontal disease status and ADCC activity in the sera of healthy subjects and patients by examining the role of antibody affinity, immunoglobulin subclass, and ELISA titer. Characterization of this model will provide the background needed to establish it as an etiologic factor in the development of periodonatal disease and will provide the impetus for further clinical evaluation, with the ultimate goal of possible pharmacologic control of the mechanism.