Project 4: PAF acetyhydrolase in localized juvenile periodontitis. Localized Juvenile Periodontitis (LJP) has a circumpurbertal onset and is characterized by severe destruction of the periodontal tissues surrounding the first molars and incisors. Although LJP has some of the clinical characterization of other periodontal diseases, it is clearly unique in terms of its mechanisms of pathogenesis and inheritance patterns. Among the immunological anomalies associated with LJP are the elevated levels of IgG 2 that are commonly found in the sera of LJP patients. Recent experiments suggest that IgG2 production is regulated by macrophage- derived lipid cytokines. Platelet activating factor (PAF), in particular stimulates IgG2 production, but has minimal effects on other isotypes of IgG. Preliminary data suggest that mononuclear cells from LJP patients express lower levels of PAF acetylhydrolase (PAF-AH), the enzyme that catabolizes PAF, then cells from periodontally healthy subjects. The decrease in PAF-AH activity could increase the availability of PAF and thereby stimulate IgG2 production in LJP patients. Hence, the goal of this research effort is elucidate the role of PAF-AH in the regulation of IgG2 production in LJP patients. Hence, the goal of this research effort is elucidate the role of PAF-AH in the regulation of IgG2 production in LJP patients. Experiments will be performed to determine whether mononuclear cells from LJP patients secrete less PAF-AH than cells from periodontally health subjects and if this enzyme is a negative regulator of IgG2 production. As preliminary studies indicate that mononuclear cells from LJP patients are predisposed to differentiate into dendritic cells, experiments will be performed to determine if dendritic cells express less PAF-AH than macrophages. Several lines of evidence indicate that both LJP and PAF-AH levels are heritable. Therefore, PAF-AH levels will be measured in the sera of LJP probands and their family members to determine if PAF-AH correlates with the incidence of the disease. Some cigarette smokers exhibit lower levels of serum IgG2 than non-smokers. This effect varies with the race and periodontal health status of the subject. Preliminary experiments indicate that there are higher levels of PAF-AH in the plasma of smokers than in non-smokers. Therefore, experiments will be performed to determine if PAF-AH is related to the reduction in serum IgG2 that is observed in cigarette smokers. Together, these studies should elucidate the role of PAF-AH in the regulation of IgG2 production. In addition, these experiments may yield insights into the genetic mature of LJP.
| Griffiths, Rachel; Barbour, Suzanne (2010) Lipoproteins and lipoprotein metabolism in periodontal disease. Clin Lipidol 5:397-411 |
