NEUTROPHIL FUNCTION IN SEVERE PERIODONTITIS SUBJECTS

严重牙周炎患者的中性粒细胞功能

• 批准号: 6104700
• 负责人: MARK E WILSON
• 金额: $ 3.21万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104700
• 关键词: Actinobacillus actinomycetemcomitans; biological signal transduction; cell adhesion molecules; chemotaxis; dental plaque; diabetes mellitus; disease /disorder proneness /risk; flow cytometry; human subject; neutrophil; oral bacteria; periodontitis; selectins; tobacco abuse

The neutrophil plays a key role in host defense against infection due to extracellular bacteria. Considerable evidence also indicates that the neutrophil is a critical element of host defense against periodontal injury initiated by bacteria in dental plaque. In order to provide such defense, adequate numbers of neutrophils must first penetrate vascular endothelium through an adhesion-dependent process. Following extra- vasation, neutrophils must migrate toward, ingest and ultimately destroy the target bacteria. Defects in neutrophil production or function often result in increased susceptibility to recurrent bacterial infection, and appear to predispose to early-onset, severe forms of periodontal disease which may arise prior to or during puberty. Susceptibility to severe periodontitis varies widely in the adult population. Cross-sectional studies conducted at the Clinical Research Center have identified certain variables associated with increased risk of severe periodontitis. Included in this group of "risk indicators" are diabetes and smoking. A key objective of studies proposed in this Clinical Research Center application is to conduct longitudinal studies necessary to establish if diabetes and/or smoking constitute true "risk factors" for development of severe periodontitis. Diabetes has long been associated with increased susceptibility to infection, attributable in part to altered neutrophil function. Neutrophil adherence, chemotaxis, phagocytosis and killing are often decreased in diabetes. Vascular changes observed in diabetes may also impede neutrophil extravasation into infected tissues. Various components of tobacco smoke have also been reported to inhibit neutrophil function. The objective of this pilot study is to determine whether apparent increases in susceptibility to periodontitis seen in diabetics or smokers are associated with impaired neutrophil function. Specific parameters to be evaluated will include a) in situ crevicular leukocyte responses to casein, b) expression of cell adhesion molecules (Mac-1/CR3, L- selectin) using anti-adhesion monoclonal antibodies in conjunction with flow cytometric techniques, c) in vitro aerobic and anaerobic bactericidal activity toward Actinobacillus actinomycetemcomitans, d) neutrophil degranulation, as determined by flow cytometric analysis of right angle light scatter, and e) chemotaxin (IL-8, fMLP)-induced signal transduction (IP3 production). Neutrophil responses will be compared in a) diabetic vs. non-diabetic periodontitis patients (balanced for smoking, microflora and age), b) smoker vs. non-smoker periodontitis patients (non-diabetic only balanced for microflora and age), and c) periodontitis subjects vs. periodontally healthy (diabetic and non- diabetic, as well as smoker and non-smoker) controls. These pilot studies are designed to provide the basis for an in-depth assessment of mechanisms by which smoking and/or diabetes impairs neutrophil-mediated defenses.

中性粒细胞在宿主防御感染中起关键作用， 胞外细菌 大量证据还表明， 中性粒细胞是宿主防御牙周炎的关键因素， 由牙菌斑中的细菌引起的损伤。 为了提供这种 防御，足够数量的中性粒细胞必须首先穿透血管 通过粘附依赖性过程与内皮细胞结合。 在额外的- 在血管扩张过程中，中性粒细胞必须迁移，摄取并最终破坏 目标细菌。 中性粒细胞产生或功能缺陷通常 导致对复发性细菌感染的易感性增加，以及 似乎易患早发性、严重的牙周病 这可能发生在青春期之前或期间。 成人对严重牙周炎的易感性差异很大 人口 在临床研究中心进行的横断面研究 中心已经确定了与风险增加相关的某些变量 严重的牙周炎 这组“风险指标”包括 糖尿病和吸烟 本研究提出的一个关键目标是 临床研究中心申请是为了进行纵向研究 有必要确定糖尿病和/或吸烟是否构成真正的“风险 严重牙周炎的发生发展的“因素”。 糖尿病长期以来 与感染易感性增加有关， 中性粒细胞功能改变。 神经元粘附，趋化性， 在糖尿病中吞噬作用和杀伤作用常常降低。 血管 在糖尿病中观察到的变化也可能阻碍中性粒细胞外渗 感染的组织。 烟草烟雾的各种成分也 据报道抑制中性粒细胞功能。 这项初步研究的目的是确定是否明显的 糖尿病患者或吸烟者对牙周炎的易感性增加 与中性粒细胞功能受损有关。 特定参数 a）原位裂隙白细胞反应 B）细胞粘附分子（Mac-1/CR 3，L- 选择素）结合使用抗粘附单克隆抗体 流式细胞术技术，c）体外需氧和厌氧 对伴放线放线杆菌的杀菌活性，d） 中性粒细胞脱粒，如通过流式细胞术分析测定的， 直角光散射，和e）趋化因子（IL-8，fMLP）诱导的信号 转导（IP 3产生）。 将比较神经元反应， a）糖尿病与非糖尿病牙周炎患者（平衡的 吸烟、微生物区系和年龄），B）吸烟者与非吸烟者牙周炎 患者（非糖尿病患者，仅微生物区系和年龄平衡），和c） 牙周炎受试者与牙周健康（糖尿病和非糖尿病）受试者 糖尿病患者以及吸烟者和非吸烟者）对照。 这些试点 研究的目的是为深入评估 吸烟和/或糖尿病损害嗜中性粒细胞介导的 的防御合作.