Abstract

PMN function is modulated by ligand binding to surface receptors, which induces transient increases in cytosolic Ca2+ mobilizes protein kinase C (PKC), and initiates PMN activation. Ca2+ signalling is altered by polyamines, which are prevalent in gingival fluid at inflamed periodontal sites. We hypothesize that polyamines significantly enhance Ca2+ mobilization in PMN and thereby modulate many essential responses to extracellular stimuli. We will test this hypothesis in vitro by examining the effects of polyamines at three levels of action: 1) Modulation of chemoattractant-induced Ca2+ mobilization, 2) Modulation of PKC translocation and phosphorylation of cell proteins, and 3) Modulation of PMN functions regulated by Ca2+ and PKC. These studies will provide a better understanding of the complex mechanisms involved in local modulation of PMN function in periodontal disease and other inflammatory disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Modified Research Career Development Award (K04)
Project #
5K04DE000338-03
Application #
2443663
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1995-07-01
Project End
2000-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Ohio State University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210

  Publications

Stehle, H W; Leblebicioglu, B; Walters, J D (2001) Short-chain carboxylic acids produced by gram-negative anaerobic bacteria can accelerate or delay polymorphonuclear leukocyte apoptosis in vitro. J Periodontol 72:1059-63
Conway, T B; Beck, F M; Walters, J D (2000) Gingival fluid ciprofloxacin levels at healthy and inflamed human periodontal sites. J Periodontol 71:1448-52
Bounds, S J; Nakkula, R; Walters, J D (2000) Fluoroquinolone transport by human monocytes: characterization and comparison to other cells of myeloid lineage. Antimicrob Agents Chemother 44:2609-14
Preshaw, P M; Schifferle, R E; Walters, J D (1999) Porphyromonas gingivalis lipopolysaccharide delays human polymorphonuclear leukocyte apoptosis in vitro. J Periodontal Res 34:197-202
Leblebicioglu, B; Walters, J (1999) Alkaline conditions accelerate polymorphonuclear leukocyte apoptosis in vitro. Infect Immun 67:2019-21
Walters, J D; Zhang, F; Nakkula, R J (1999) Mechanisms of fluoroquinolone transport by human neutrophils. Antimicrob Agents Chemother 43:2710-5
Ratasirayakorn, W; Leone, P; Leblebicioglu, B et al. (1999) Polyamines found in the inflamed periodontium inhibit priming and apoptosis in human polymorphonuclear leukocytes. J Periodontol 70:179-84
Walters, J D; Cario, A C; Danne, M M et al. (1998) An inhibitor of ornithine decarboxylase antagonizes superoxide generation by primed human polymorphonuclear leukocytes. J Inflamm 48:40-6
Loo, K C; Cario, A C; Zhang, F et al. (1997) Regulation of ciprofloxacin uptake in human promyelocytic leukemia cells and polymorphonuclear leukocytes. J Leukoc Biol 61:619-23
Leblebicioglu, B; Lim, J S; Cario, A C et al. (1996) pH changes observed in the inflamed gingival crevice modulate human polymorphonuclear leukocyte activation in vitro. J Periodontol 67:472-7