There is general agreement in the literature that the polymorphonuclear leukocyte (PMN) is the prominant cell type during all phases of periodontal health and disease. The importance of the PMN in the maintenance of periodontal health is suggested by the severe inflammation and periodontal destruction observed in patients with systemic PMN defects. The exact role for PMNs on a cellular basis is not will understood. They are considered to be protective against infection and exert this function presumably by phagocytosis, antibody dependent killing, and release of antimicrobial substances. Despite the association between neutrophil defects and severe periodontal disease, no clear association between neutrophil dysfunction and susceptibility has been established for Advanced Adult Periodontitis (A.A.P.), a chronic disease characterized by severe, generalized inflammation, bone loss and early tooth loss. Bacteriodes gingivalis has been implicated as an etiologic agent of A.A.P. Based on the current literature, it is not clear what role PMNs play in defense against B. gingivalis. It is possible that there may be subtle neutrophil dysfunction in dealing with this pathogen, associated with susceptibility to A.A.P. The proposed studies are therefore intended to begin to define the nature of the PMN interaction with B. gingivalis. Initial studies will examine the ability of peripheral blood neutrophil from normal patients to phagocytize and kill B. gingivalis. The role of antibody (and complement) in this process will be defined, and further characterized by an enzyme linked immunoadsorbent assay (ELISA) utilizing patient sera and killed B. gingivalis organisms to determine responsible isotypes. Antigen specificity will be elucidated by SDS-PAGE and trans-immunoblotting. The possible involvement of oxygen dependent mechanisms of killing of B. gingivalis by neurtophils will be determined and may involve myeloperoxidase (MPO), lactoferrin (LF), H202, hydroxy radical, singlet oxygen and superoxide production, and may occur intracellularly and extracellularly. Non-oxygen dependent mechanisms, involving lysozyme, lactoferrin, cationic proteins and small peptides will also be examined and may be contributory. Although nothing in the literature suggests any innate defect in A.A.P. patient neurtorphils, most studies used unrelated bacteria at test organisms. Phase II will focus on comparing the abilities of normal and patient neutorphils to phagocytize and kill B. gingivalis, while examining degranulation, superoxide production and chemotaxis to complete this profile.
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