The neutrophil plays a key role in host defense against infection due to extracellular bacteria. Considerable evidence also indicates that the neutrophil is a critical element of host defense against periodontal injury initiated by bacteria in dental plaque. In order to provide such defense, adequate numbers of neutrophils must first penetrate vascular endothelium through an adhesion-dependent process. Following extra- vasation, neutrophils must migrate toward, ingest and ultimately destroy the target bacteria. Defects in neutrophil production or function often result in increased susceptibility to recurrent bacterial infection, and appear to predispose to early-onset, severe forms of periodontal disease which may arise prior to or during puberty. Susceptibility to severe periodontitis varies widely in the adult population. Cross-sectional studies conducted at the Clinical Research Center have identified certain variables associated with increased risk of severe periodontitis. Included in this group of """"""""risk indicators"""""""" are diabetes and smoking. A key objective of studies proposed in this Clinical Research Center application is to conduct longitudinal studies necessary to establish if diabetes and/or smoking constitute true """"""""risk factors"""""""" for development of severe periodontitis. Diabetes has long been associated with increased susceptibility to infection, attributable in part to altered neutrophil function. Neutrophil adherence, chemotaxis, phagocytosis and killing are often decreased in diabetes. Vascular changes observed in diabetes may also impede neutrophil extravasation into infected tissues. Various components of tobacco smoke have also been reported to inhibit neutrophil function. The objective of this pilot study is to determine whether apparent increases in susceptibility to periodontitis seen in diabetics or smokers are associated with impaired neutrophil function. Specific parameters to be evaluated will include a) in situ crevicular leukocyte responses to casein, b) expression of cell adhesion molecules (Mac-1/CR3, L- selectin) using anti-adhesion monoclonal antibodies in conjunction with flow cytometric techniques, c) in vitro aerobic and anaerobic bactericidal activity toward Actinobacillus actinomycetemcomitans, d) neutrophil degranulation, as determined by flow cytometric analysis of right angle light scatter, and e) chemotaxin (IL-8, fMLP)-induced signal transduction (IP3 production). Neutrophil responses will be compared in a) diabetic vs. non-diabetic periodontitis patients (balanced for smoking, microflora and age), b) smoker vs. non-smoker periodontitis patients (non-diabetic only balanced for microflora and age), and c) periodontitis subjects vs. periodontally healthy (diabetic and non- diabetic, as well as smoker and non-smoker) controls. These pilot studies are designed to provide the basis for an in-depth assessment of mechanisms by which smoking and/or diabetes impairs neutrophil-mediated defenses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Specialized Center (P50)
Project #
5P50DE004898-19
Application #
5210088
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
1996
Total Cost
Indirect Cost
LaMonte, Michael J; Williams, AnnaLynn M; Genco, Robert J et al. (2014) Association between metabolic syndrome and periodontal disease measures in postmenopausal women: the Buffalo OsteoPerio study. J Periodontol 85:1489-501
LaMonte, Michael J; Hovey, Kathleen M; Millen, Amy E et al. (2014) Accuracy of self-reported periodontal disease in the Women's Health Initiative Observational Study. J Periodontol 85:1006-18
LaMonte, Michael J; Hovey, Kathleen M; Genco, Robert J et al. (2013) Five-year changes in periodontal disease measures among postmenopausal females: the Buffalo OsteoPerio study. J Periodontol 84:572-84
Bole, Christopher; Wactawski-Wende, Jean; Hovey, Kathleen M et al. (2010) Clinical and community risk models of incident tooth loss in postmenopausal women from the Buffalo Osteo Perio Study. Community Dent Oral Epidemiol 38:487-97
Brennan-Calanan, R M; Genco, R J; Wilding, G E et al. (2008) Osteoporosis and oral infection: independent risk factors for oral bone loss. J Dent Res 87:323-7
Brennan, Renee M; Genco, Robert J; Wilding, Gregory E et al. (2007) Bacterial species in subgingival plaque and oral bone loss in postmenopausal women. J Periodontol 78:1051-61
Brennan, Renee M; Genco, Robert J; Hovey, Kathleen M et al. (2007) Clinical attachment loss, systemic bone density, and subgingival calculus in postmenopausal women. J Periodontol 78:2104-11
Genco, Robert J; Falkner, Karen L; Grossi, Sara et al. (2007) Validity of self-reported measures for surveillance of periodontal disease in two western New York population-based studies. J Periodontol 78:1439-54
Tezal, Mine; Scannapieco, Frank A; Wactawski-Wende, Jean et al. (2006) Supragingival plaque may modify the effects of subgingival bacteria on attachment loss. J Periodontol 77:808-13
Sojar, Hakimuddin T; Genco, Robert J (2005) Identification of glyceraldehyde-3-phosphate dehydrogenase of epithelial cells as a second molecule that binds to Porphyromonas gingivalis fimbriae. FEMS Immunol Med Microbiol 45:25-30

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