PAF ACETYL-HYDROLASE IN LOCALIZED JUVENILE PERIODONTITIS

项目4：局部青少年牙周炎的PAF乙酰水解酶。局限性青少年牙周炎（LJP）是一种以第一磨牙和门牙周围牙周组织严重破坏为特征的疾病。虽然LJP具有其他牙周病的一些临床特征，但其发病机制和遗传模式显然是独特的。在与LJP相关的免疫异常中，IgG 2水平升高是LJP患者血清中常见的。最近的实验表明，IgG2的产生受巨噬细胞衍生的脂质细胞因子的调节。血小板活化因子（PAF），特别是刺激IgG2的产生，但对其他同型IgG的影响最小。初步数据表明，牙周jp患者的单核细胞表达较低水平的PAF乙酰水解酶（PAF- ah）， PAF是分解PAF的酶，而来自牙周健康受试者的细胞表达较低水平。PAF- ah活性的降低可以增加PAF的可用性，从而刺激LJP患者IgG2的产生。因此，本研究的目的是阐明PAF-AH在LJP患者中调节IgG2产生的作用。因此，本研究的目的是阐明PAF-AH在LJP患者中调节IgG2产生的作用。实验将确定LJP患者的单核细胞是否比牙周健康者的细胞分泌更少的PAF-AH，以及这种酶是否是IgG2产生的负调节因子。由于初步研究表明LJP患者的单核细胞倾向于分化为树突状细胞，因此将进行实验以确定树突状细胞是否比巨噬细胞表达更少的PAF-AH。一些证据表明LJP和PAF-AH水平都是可遗传的。因此，将测定LJP先证者及其家庭成员血清中PAF-AH水平，以确定PAF-AH是否与该病的发病率相关。一些吸烟者的血清IgG2水平低于不吸烟者。这种效果随受试者的种族和牙周健康状况而异。初步实验表明，吸烟者血浆中PAF-AH的含量高于非吸烟者。因此，将进行实验来确定PAF-AH是否与在吸烟者中观察到的血清IgG2降低有关。总之，这些研究应该阐明PAF-AH在调节IgG2产生中的作用。此外，这些实验可能对LJP的遗传成熟有深入的了解。

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.