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.
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