P. gingivalis Capsule in Cell Inflammation

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DESCRIPTION: Porphyromonas gingivalis, a Gram-negative, anaerobic, oral pathogen is the primary etiologic agent of adult periodontal disease. Recent reports indicate that encapsulated P. gingivalis are more virulent then unencapsulated strains. Nevertheless, the precise role of P. gingivalis capsular polysaccharide in disease pathogenesis, and the mechanism by which this virulence factor acts, are largely unknown. We posit that the capsular polysaccharide of Porphyromonas gingivalis promotes a cellular inflammatory response characteristic of P. gingivaIis infection, and contributes to the pathology observed in P. gingivalis-mediated adult periodontal disease. Our preliminary, in vitro studies demonstrate that this antigen binds to host cells and stimulates an innate immune response, which is permissive for PMN chemotaxis. In vivo observations confirmed our in vitro data, and demonstrate that purified P. gingivalis capsular polysaccharide stimulates a host inflammatory cell response, that mimics live, P. gingivalis whole cell challenge. Three Specific Aims are proposed: 1): To define the binding kinetics of purified Porphyromonas gingivalis capsular polysaccharide to epithelial cells and defined populations of relevant immune cells. We will characterize 1- dose-and time-dependent binding kinetics, 2- binding specificity, and employ blocking studies to define the attachment of purified P. gingivalis capsular polysaccharide to host cells. 2): To characterize the innate immune response of epithelial cells and relevant leukocyte populations to P. gingivalis capsular polysaccharide. Cytokine secretion, cell adhesion molecule production and neutrophil recruitment will be examined. We will delineate the cytokine, chemokine and cell adhesion molecule repertoire produced by cells challenged as related to stimulation and characterization of PMN transmigration. 3): To define the cellular inflammatory event that occurs in response to Porphyromonas gingivalis capsular polysaccharide in a murine air pouch model. We will characterize the host cellular inflammatory response to purified P. gingivalis capsular polysaccharide and begin to define the innate immune responses that govern leukocyte recruitment.