Actinobacillus actinomycetemcomitans (Aa) and Bacteroides gingivalis (Bg) have implicated in the etiology of certain forms of periodontal disease. It has been suggested that the neutrophil plays a primary role in the defense against establishment of these purported periodontopathogens. The overall objective of this proposed work is to define the mechanisms of the PMN involved in the defense against periodontal diseases by examining and defining the functional defects of patients with periodontal disease. It is well established that the PMN of patients with localized juvenile periodontitis (LJP) have quantitative chemotactic defects. Preliminary studies with LJP PMN suggest they are capable of normal phagocytoses of Aa; however, they fail to kill these organisms. These studies will, therefore, examine the LJP PMN to determine the underlying dysfunction that results in this inability to kill Aa. It will first be determined if this dysfunction is specific or a generalized deficiency in killing of all microorganisms by examining LJP PMN of their ability to kill not only Aa, but also Bg, Staphylococcus aureus, Escherichia coli, and Streptococcus mutans. The bactericidal activity of the LJP PMN will be compared with that of healthy controls, and of patients with chronic adult or refractory periodontitis in the presence and absence of patient and control sera and saliva. Recent studies indicate that there are distinct subsets of PMN granules that may constitute functionally distinct populations. A quantitative or qualitative defect in one or more of these granule subsets may result in an inability to kill a specific microoganisms or group of microoganisms. The granule profiles obtained by isopycnic gradient centrifugation of fractions of patient and control PMN will be compared using biochemical analyses for selected granule markers. In addition, the granule content and supernatants of the various cell populations will be examined following stimulation with opsonized test organisms or specific secretogogues. It is further proposed to study the functional abilities of 1gA-Fc receptor positive subpopulation of PMN and their influence by serum and secretory antibodies. The surface characteristics of 1gA+ and 1gA- PMNs will be characterized using other ligands as probes of membrane structure by direct binding assays. A study of these patient populations offers a unique opportunity to dissect the functional roles of subsets of PMN granules and enzymes and subset populations of cells in relation to susceptibility to specific periodontopathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE007808-02
Application #
3221595
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1987-09-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Genco, C A; Kapczynski, D R; Cutler, C W et al. (1992) Influence of immunization on Porphyromonas gingivalis colonization and invasion in the mouse chamber model. Infect Immun 60:1447-54
Cutler, C W; Kalmar, J R; Arnold, R R (1991) Antibody-dependent alternate pathway of complement activation in opsonophagocytosis of Porphyromonas gingivalis. Infect Immun 59:2105-9
Cutler, C W; Kalmar, J R; Arnold, R R (1991) Phagocytosis of virulent Porphyromonas gingivalis by human polymorphonuclear leukocytes requires specific immunoglobulin G. Infect Immun 59:2097-104
Cutler, C W; Eke, P; Arnold, R R et al. (1991) Defective neutrophil function in an insulin-dependent diabetes mellitus patients. A case report. J Periodontol 62:394-401
Genco, C A; Cutler, C W; Kapczynski, D et al. (1991) A novel mouse model to study the virulence of and host response to Porphyromonas (Bacteroides) gingivalis. Infect Immun 59:1255-63
Van Dyke, T E; Hoop, G A (1990) Neutrophil function and oral disease. Crit Rev Oral Biol Med 1:117-33
Kalmar, J R; Arnold, R R (1988) Killing of Actinobacillus actinomycetemcomitans by human lactoferrin. Infect Immun 56:2552-7
Kalmar, J R; Arnold, R R; Warbington, M L et al. (1988) Superior leukocyte separation with a discontinuous one-step Ficoll-Hypaque gradient for the isolation of human neutrophils. J Immunol Methods 110:275-81