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

本课题从细胞内信号转导机制的角度分析了早发性牙周炎患者中性粒细胞趋化功能下降的机制。我们分析了外周血中性粒细胞受基因限制的趋化抑制机制，以及宿主-寄生虫相互作用可能发生在局部牙周区的研究模型。首先，我们使用一个新的临床参数来评估外周中性粒细胞的趋化性与牙周病进展之间的关系。可将患者分为两组：1)中性粒细胞趋化功能低下和其他中性粒细胞反应异常的患者；2)中性粒细胞趋化功能正常和伴放线放线杆菌(AA)严重感染的患者。前者受基因限制，后者是AA与中性粒细胞相互作用的结果。分析了1)外周血中中性粒细胞的异常反应，即…2)再生障碍性贫血白细胞毒素对白细胞信号转导的影响。主要研究内容包括：1.中性粒细胞趋化作用在晚期牙周炎中的作用；2.幼年牙周炎患者中性粒细胞趋化功能下降及其信号转导机制；1)幼年牙周炎患者中性粒细胞蛋白激酶C活性；2)趋化因子刺激下细胞内钙离子浓度的变化；3)早发性牙周炎细胞表面CD18分子表达不足；3.再生障碍性牙周炎白毒素的细胞毒作用机制。青少年牙周炎患者中性粒细胞中蛋白激酶C活性较低。AA产生的白毒素可促进HL-60细胞110 kDa蛋白的钙依赖性磷酸化。临床状态相似的牙周炎，即使在同一个家族中，也不一定具有相同的宿主防御细胞紊乱。从细胞功能、生物活性分子、基因等方面进一步阐明牙周病发生机制的多态现象。较少

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