Our previous investigations have demonstrated that crevicular fluid prostaglandin E2 (CF-PGE) levels can reflect ongoing, subclinical periodontal tissue destruction in a site-specific manner. This sensitive and reliable diagnostic tool will be utilized to provide a biochemical definition of periodontal sites which are """"""""active"""""""" or """"""""inactive"""""""" with regard to disease progression. This will enable the study of the biochemical basis of periodontal disease progression. This proposal seeks to examine the role of the arachidonic acid (ARA) metabolites in the pathogenesis of chronic gingivitis, adult and juvenile periodontitis. Comparisons of local tissue levels of key metabolites will be performed on 60 diseased patients (20 each category), sampling diseased sites and comparing to non-inflamed sites within each patient. Tissues from ten healthy individuals will also be analyzed. ARA metabolites will be extracted from tissue samples, chromatographed, separated, quantitated and identified by RIA or GC/MS. Emphasis will be placed on the simultaneous detection of the leukotrienes B4, C4, D4, E4 and PGE2, PGI2, TxA2 and PGF2 alpha. These key inflammatory mediators will be determined in biochemically defined """"""""active"""""""" and """"""""inactive"""""""" lesions in periodontitis patients, as well as at sites which demonstrate significant longitudinal attachment loss. This will determine which of the key metabolites are involved in the disease progression. Leukotrienes (LTs) are the principal ARA metabolites of neutrophils. The level present within the inflamed periodontal tissues appears to mimic that produced by calcium ionophore-stimulated peripheral blood neutrophils for each particular individual. This relationship will be investigated in the 60 patients and matched healthy controls to determine if neutrophil secretion of LTs in culture can be used to identify disease status or patients at risk. This hypothesis is supported by the observation that neutrophils from juvenile periodontitis (JP) patients have impaired net synthesis of LTB4 as compared to normal. The third line of investigation will determine which of the three key synthetic enzymes (5 lipoxygenase, LTA4 synthetase and LTB4 synthetase) is defective in JP neutrophils. This will be done using 14C ARA or 14C 5HPETE and determining end product distribution in ionophore-stimulated neutrophil cultures.
| Offenbacher, S; Heasman, P A; Collins, J G (1993) Modulation of host PGE2 secretion as a determinant of periodontal disease expression. J Periodontol 64:432-44 |
| Offenbacher, S; Collins, J G; Heasman, P A (1993) Diagnostic potential of host response mediators. Adv Dent Res 7:175-81 |
| Orkin, J L; Braswell, L D (1990) Sialolithiasis in two chimpanzees. J Am Vet Med Assoc 196:1651-3 |
