Polymorphonuclear leukocytes (PMNs) are the infantry of the cellular host defense system. In response to infections PMNs exhibit an increase in a sequence of cell functions which include: adhesion, chemotaxis, phagocytosis, degranulation, and ultimately bacterial killing. The first four of these responses involve cell motility, and therefore depend on continued, orderly, long-term reorganizations of the actin cytoskeleton. Accumulating data indicate that receptor-ligand interactions initiate these cellular responses. Furthermore, the very early events following receptor-ligand interaction include an immediate, rapid, transient, alteration in the actin cytoskeleton and intracellular pH. In separate but related literature, clinical data indicate that anaerobic bacteria which are thought to cause periodonatal infections release short chain fatty acids. (SCFA) into their environment. These SCFA have been shown to inhibit PMN motile functions. We are therefore interested in answering the following molecular questions: 1. Do SCFAs alter the PMN actin cytoskeleton? 2. Do SCFAs alter the internal pH of the PMN? and 3. Do SCFAs alter PMN chemotactic peptide receptors? If the results of the proposed work indicate that the SCFAs do have a deleterious effect on PMNs, several additional questions will be of great clinical interest: What SCFAs are present in sites with active periodontitis? What is the effect of SCFA on other cells of the periodontium? and finally, Can bacterial cells be engineered which have reduced SCFA production?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE008415-02
Application #
3222117
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1988-06-01
Project End
1991-05-31
Budget Start
1989-06-01
Budget End
1990-05-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Forsyth Institute
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Kashket, S; Zhang, J; Niederman, R (1998) Gingival inflammation induced by food and short-chain carboxylic acids. J Dent Res 77:412-7
Sorkin, B C; Niederman, R (1998) Short chain carboxylic acids decrease human gingival keratinocyte proliferation and increase apoptosis and necrosis. J Clin Periodontol 25:311-5
Swartwout, S; Niederman, R (1997) Bacterial metabolite mediated differential human PMN gene expression. J Periodontal Res 32:196-9
Niederman, R; Zhang, J; Kashket, S (1997) Short-chain carboxylic-acid-stimulated, PMN-mediated gingival inflammation. Crit Rev Oral Biol Med 8:269-90
Niederman, R; Buyle-Bodin, Y; Lu, B Y et al. (1997) Short-chain carboxylic acid concentration in human gingival crevicular fluid. J Dent Res 76:575-9
Kandikonda, S; Oda, D; Niederman, R et al. (1996) Cadherin-mediated adhesion is required for normal growth regulation of human gingival epithelial cells. Cell Adhes Commun 4:13-24
Kashket, S; Zhang, J; Van Houte, J (1996) Accumulation of fermentable sugars and metabolic acids in food particles that become entrapped on the dentition. J Dent Res 75:1885-91
Niederman, R; Buyle-Bodin, Y; Lu, B Y et al. (1996) The relationship of gingival crevicular fluid short chain carboxylic acid concentration to gingival inflammation. J Clin Periodontol 23:743-9
Niederman, R; Naleway, C; Lu, B Y et al. (1995) Subgingival temperature as a gingival inflammatory indicator. J Clin Periodontol 22:804-9
Papapanou, P N; Sandros, J; Lindberg, K et al. (1994) Porphyromonas gingivalis may multiply and advance within stratified human junctional epithelium in vitro. J Periodontal Res 29:374-5

Showing the most recent 10 out of 18 publications