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作用。局限性青少年牙周炎（LJP）是一种以第一磨牙和切牙周围的牙周组织严重破坏为特征的牙周病。虽然LJP具有其他牙周病的一些临床特征，但就其发病机制和遗传模式而言，它显然是独特的。在与LJP相关的免疫异常中，通常在LJP患者血清中发现IgG 2水平升高。最近的实验表明，IgG 2的产生是由巨噬细胞衍生的脂质细胞因子调节的。血小板活化因子（PAF），特别是刺激IgG 2的生产，但对其他同种型的IgG的影响很小。初步数据表明，LJP患者的单核细胞表达较低水平的PAF乙酰水解酶（PAF-AH），分解代谢PAF的酶，然后牙周健康受试者的细胞。PAF-AH活性的降低可增加PAF的利用率，从而刺激LJP患者IgG 2的产生。因此，本研究的目的是阐明PAF-AH在LJP患者IgG 2产生调节中的作用。因此，本研究的目的是阐明PAF-AH在LJP患者IgG 2产生调节中的作用。将进行实验以确定来自LJP患者的单核细胞是否比来自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IgG 2产生的负调节剂。由于初步研究表明，来自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表达的PAF-AH是否低于巨噬细胞。几条证据表明LJP和PAF-AH水平都是可遗传的。因此，将在LJP先证者及其家族成员的血清中测量PAF-AH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IgG 2水平低于非吸烟者。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，吸烟者血浆中的PAF-AH水平高于非吸烟者。因此，将进行实验以确定PAF-AH是否与吸烟者中观察到的血清IgG 2降低相关。总之，这些研究应阐明PAF-AH在调节IgG 2产生中的作用。此外，这些实验可能会产生洞察LJP的遗传成熟。

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.