Faculty Bibliography

Infections of the dental pulp commonly result in infraosseus inflammation and bone destruction. However, the role of phagocytic leucocytes in the pathogenesis of pulpal infections has been uncertain. In this work we used P/E-/- selectin-deficient mice, which lack rolling adhesion of leucocytes to endothelium and mimic the human syndrome, leucocyte adhesion deficiency II (LAD-II), to test the hypothesis that phagocytic leucocytes protect against pulpal infection and subsequent periapical infraosseus bone resorption. P/E-/- mice and P/E+/+ wild-type controls were subjected to surgical pulp exposure, and both groups were infected with a mixture of pulpal pathogens including Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococcus micros and Streptococcus intermedius. Animals were killed after 20 days, and the extent of infraosseus bone destruction was quantified by histomorphometry. In two separate experiments, P/E-/- mice had significantly greater bone resorption than P/E+/+ controls. The increased bone destruction correlated with a twofold decrease in polymorphonuclear (PMN) infiltration into periapical inflammatory tissues of P/E-/- mice. P/E-/- mice had higher tissue levels of the bone resorptive cytokine, interleukin (IL)-1alpha. Tissue levels of IL-2, IL-4, IL-10, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were all higher in P/E-/- mice, but the increases were not statistically significant. Only IL-12 was higher in P/E+/+ mice, possibly reflecting a greater number of infiltrating monocytes in wild-type mice. These findings demonstrate that phagocytic leucocytes are protective in this model, and suggest that elevated expression of inflammatory cytokines is responsible for the observed bone destruction.

Epithelia are key barriers to infections. In periodontal disease, the gingival sulcular epithelium becomes ulcerated. In this report, we test the hypothesis that short-chain carboxylic acids (SCCA) inhibit keratinocyte proliferation, increase necrosis and apoptosis, and may thus promote ulceration. SCCA produced by bacteria are present at millimolar concentrations in the periodontal pockets of subjects with periodontal disease. SCCA concentrations are higher in subjects with severe disease than in those with mild disease, and are not detectable in healthy subjects. Cell proliferation is critical for maintenance of epithelial barrier function. All SCCA tested, when neutralized, decreased epithelial cell proliferation (as measured by 3H-thymidine incorporation) in a dose-dependent manner. We found that epithelial cell viability decreased with increasing SCCA concentrations, accounting at least partly for the decreased 3H-thymidine incorporation. For all conditions we tested, SCCA-induced apoptosis preceded and exceeded necrosis. While the molecular mechanism(s) for these effects remain to be determined, the results indicate that SCCA derived from caries- or periodontal disease-associated bacteria could alter gingival barrier function.

Earlier studies in our laboratories demonstrated that particles of a number of snack foods that are retained on the dentition accumulate fermentable sugars and short-chain carboxylic acids (SCCA; acetic, formic, lactic, and propionic) to different degrees. The present study was undertaken to test the hypothesis that the accumulated SCCA can induce a gingival inflammatory response. Five periodontally and medically healthy subjects were given portions of plain doughnuts (high SCCA levels) or oatmeal cookie (low SCCA), or had the SCCA applied directly to the gingival margins of designated teeth. Subjects were given wax to chew, or nothing, as controls. Inflammation was assessed by measurements of subgingival temperature, flow rates of gingival crevicular fluid (GCF), and neutrophil emigration into GCF. Subgingival temperatures of the maxillary gingiva rose by 1.32 +/- 0.30 degrees C (mean +/- SE) 5 min after the subjects consumed the doughnuts and remained elevated for at least 1 hr. These values were significantly higher than those obtained from subjects after ingestion of oatmeal cookies (0.63 +/- 0.17 degree C; p < 0.01), consistent with the low levels of SCCA in the retained cookie particles. Wax chewing elicited a similar response, indicating a masticatory effect on the gingiva. Gingival temperatures in the unchallenged controls remained unchanged. Neutrophil emigration into the GCF was significantly elevated in subjects after doughnut consumption. Rinses with a solution of SCCA, or application of the SCCA to the gingiva, also brought about significant elevations in subgingival temperature and neutrophil emigration. The findings describe the inflammatory effects of food ingestion on the gingiva of healthy human subjects, and support the hypothesis that SCCA in the particles of retained food are at least partly responsible for the observed responses.