Studies on signal transduction of neutrophils from early-onset periodonititis patients

早发性牙周炎患者中性粒细胞信号转导研究

• 批准号: 05454516
• 负责人: KURIHARA Hidemi
• 金额: $ 3.9万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454516/
• 关键词: Protein kinase C; Cyclic AMP; CD18; CD11; Intracellular calucium ion; Phosphorylation; Leukotoxin; A.actinomycetemcomitans; 若年性歯周炎; 好中球; 走化能; プロテインキナーゼC; LFA-1; FMLP; cAMP

In this project, we analyzed themechanism of depressed neutrophil chemotaxis in patients with early-onset periodontitis from the standpoint of intracellular signal transduction mechanism. We analyzed both of depressed chemotaxis mechanism in peripheral blood neutrophil, that genetically restricted, and in a study model that might be occurred in local periodontal region as the result of host-parasite interaction. Firstly, we evaluated the association between chemotaxis of peripheral neutrophils and the progression of periodontal disease with using a new clinical parameter. We could classify the patients into two groups ; 1) patients with depressed neutrophil chemotaxis and other abnormal reaction of neutrophil and 2) patients with normal neutrophil chemotaxis and severe A.actinomycetemcomitans (Aa) infection. Former is restricted genetically and later is the result from the interaction between Aa and neutrophils. Then, we analyzed 1) the abnormal reaction of peripheral neutrophils, that … More restricted genetically, from the stand points of intracellular signal transduction and 2) the influences on signal transduction of leukocytes by leukotoxin from Aa. The main project tittles were 1. the role of neutrophil chemotaxis on advanced periodontitis, 2. depressed neutrophil chemotaxis and the signal transduction mechanism in juvenile periodontitis, i) protein kinase C activity in neutrophils from juvenile periodontitis patients, ii) the change of intracellular concentration of calcium ion with stimulation of chemoattractant, iii) the deficient expression of CD18 molecule on cell surface in early-onset periodontitis, 3. the mechanism of cytotoxity of leukotoxin from Aa. Protein kinase C activity was low in the neutrophils from juvenile periodontitis patients. Deficient CD18 expression was not caused by anomaly on the genomic DNA.leukotoxin from Aa enhances the calcium dependent phosphorylation of 110 kDa protein of HL-60 cell. Periodontitis with similar clinical status not always have the same disorder of host defensive cells even in the same family. We have to further clarify the polymorphism on mechanism of development of periodontal disease at cellular functions, bioactive molecules, and genes. Less

本课题从细胞内信号转导机制的角度分析早发性牙周炎患者中性粒细胞趋化性降低的机制。我们分析了受遗传限制的外周血中性粒细胞的抑制趋化机制，以及作为宿主-寄生虫相互作用的结果可能发生在局部牙周区域的研究模型。首先，我们使用一个新的临床参数来评估外周血中性粒细胞趋化性与牙周病进展之间的关系。我们将患者分为两组：1）中性粒细胞趋化性降低和其他中性粒细胞异常反应的患者; 2）中性粒细胞趋化性正常和伴放线放线菌（Aa）严重感染的患者。前者受遗传因素的限制，后者是Aa与中性粒细胞相互作用的结果。然后，我们分析了1）外周血中性粒细胞的异常反应， ...更多信息 从细胞内信号转导的角度探讨了Aa白细胞毒素对白细胞信号转导的影响。主要项目的标题是1。中性粒细胞趋化性在晚期牙周炎中的作用; 2.青少年牙周炎患者中性粒细胞趋化性降低及其信号转导机制，青少年牙周炎患者中性粒细胞蛋白激酶C活性，趋化因子刺激后细胞内钙离子浓度的变化，早发性牙周炎患者细胞表面CD 18分子表达不足，3. Aa白细胞毒素的细胞毒作用机制。青少年牙周炎患者中性粒细胞蛋白激酶C活性较低。Aa白细胞毒素可增强HL-60细胞110 kDa蛋白的钙依赖性磷酸化。临床表现相似的牙周炎，即使在同一家系中，也不一定存在相同的宿主防御细胞紊乱。牙周病发生发展的细胞功能、生物活性分子和基因多态性机制有待进一步阐明。少

项目成果

Takahashi,K.,et al.: "Clinical and laboratory studies on a patient with rapidly progressive periodontitis and their family members.A case report." J Periodontol. 66 (in press). (1995)

Takahashi,K.,et al.：“对快速进展性牙周炎患者及其家人的临床和实验室研究。病例报告。”

Murayama,Y.,et al.: "Leukocyte adhesion molecules CD11/CD18 and their role;In Molecular Pathogeneses of Periodontal Disease(Genco,R,Hamada,S.,Lehner,T.,McGhee.,J.,Mergenhagen,S.,editors)." American Society for Microbiology,Washington D.C., 215-233 (1994)

Murayama, Y., et al.：“白细胞粘附分子 CD11/CD18 及其作用；牙周病的分子发病机制（Genco,R,Hamada,S.,Lehner,T.,McGhee.,J.,Mergenhagen,S）

Murayama,Y.et al.: "Leukocyte adhesion molecules CD11/CD18 and their role:In Molecular (Genco R.,Hamada S.,Lehner T.,McGhee J.,Mergenhagen S.,editors)" American Society for Microbiology, Washington D.C., 215-233 (1994)

Murayama, Y. 等人：“白细胞粘附分子 CD11/CD18 及其作用：分子（Genco R.、Hamada S.、Lehner T.、McGhee J.、Mergenhagen S.，编辑）”美国微生物学会，

Takahashi, K.: "Clinical and laboratory studies on a patient with rapidly progressive periodontitis and their family members.A case report." J Periodontol. 66. (in press) (1995)

Takahashi, K.：“对一名快速进展性牙周炎患者及其家人的临床和实验室研究。病例报告。”

葛城 教子: "早期発症型歯周炎を有する1家族の症例研究-宿主細菌相互作用の観点から-" 日本歯科保存学雑誌. 36. 1848-1858 (1993)

Noriko Katsuragi：“一个早发性牙周炎家庭的案例研究 - 从宿主-细菌相互作用的角度”日本保守牙科杂志 36. 1848-1858 (1993)。