PAF ACETYL-HYDROLASE IN LOCALIZED JUVENILE PERIODONTITIS

项目4：PAF乙酰水解酶在局限性青少年牙周炎中的应用。局限性青少年牙周炎(LJP)以第一磨牙和门牙周围牙周组织严重破坏为特征。虽然LJP具有其他牙周病的一些临床特征，但在发病机制和遗传模式方面明显是独一无二的。在与LJP相关的免疫异常中，LJP患者血清中常见的IgG2水平升高。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。尤其是血小板激活因子(PAF)能刺激IgG2的产生，但对其他类型的免疫球蛋白影响很小。初步数据表明，LJP患者的单个核细胞表达PAF乙酰水解酶(PAF-AH)水平较低，PAF-AH是一种分解PAF的酶，而牙周健康受试者的细胞则表达较低水平的PAF-AH。PAF-AH活性降低可增加PAF的利用率，从而刺激LJP患者产生IgG2。因此，这项研究的目的是阐明PAF-AH在LJP患者IgG2产生调节中的作用。因此，这项研究的目的是阐明PAF-AH在LJP患者IgG2产生调节中的作用。将进行实验，以确定LJP患者的单核细胞是否比牙周健康受试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患者的单个核细胞易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的水平，以确定PAF-AH是否与疾病的发病率相关。一些吸烟者的血清IgG2水平低于不吸烟者。这种影响因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水平高于非吸烟者。因此，将进行实验以确定PAF-AH是否与吸烟者观察到的血清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的遗传成熟有更深入的了解。

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.