NEUTROPHIL FUNCTION IN SEVERE PERIODONTITIS SUBJECTS

中性粒细胞在宿主抵抗感染中起着关键作用 胞外细菌。大量证据还表明， 中性粒细胞是宿主防御牙周的关键因素 牙菌斑中的细菌引起的损伤。为了提供这样的服务 防御，必须首先有足够数量的中性粒细胞穿透血管 内皮细胞通过黏附依赖的过程。以下是额外的- 血管，中性粒细胞必须向外迁移，摄取并最终摧毁 目标细菌。中性粒细胞的生产或功能缺陷 导致对反复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青春期期间。 成人对严重牙周炎的易感性差异很大。 人口。在临床研究中进行的横断面研究 中心已经确定了某些与风险增加相关的变量 严重的牙周炎。这组“风险指标”包括 糖尿病和吸烟。在这项研究中提出的一个关键目标 临床研究中心的申请是进行纵向研究 有必要确定糖尿病和/或吸烟是否构成真正的“风险” 导致严重牙周炎的“因素”。糖尿病长期以来 与感染易感性增加有关，可归因于 部分原因是中性粒细胞功能改变。中性粒细胞黏附，趋化性， 糖尿病患者的吞噬功能和杀伤力通常降低。血管 糖尿病患者观察到的变化也可能阻碍中性粒细胞外渗 进入受感染的组织。烟草烟雾的各种成分也 据报道有抑制中性粒细胞功能的作用。 这项初步研究的目标是确定明显的 糖尿病或吸烟者患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 要评估的内容包括：a)原位裂隙白细胞反应 对于酪蛋白，b)细胞黏附分子(Mac-1/CR3，L- 选择素)结合使用抗黏附单抗 流式细胞仪技术，c)体外需氧和厌氧 对伴生放线杆菌的杀菌活性 用流式细胞术分析测定中性粒细胞脱颗粒 直角光散射和趋化因子(IL-8，fMLP)诱导的信号 转导(IP3产生)。中性粒细胞的反应将在 A)糖尿病牙周炎患者与非糖尿病牙周炎患者(平衡 吸烟、微生物区系和年龄)，b)吸烟者与不吸烟者牙周炎 患者(非糖尿病患者仅平衡微生物区系和年龄)，以及c) 牙周炎受试者与牙周健康者(糖尿病患者和非牙周病患者 糖尿病，以及吸烟者和不吸烟者)对照。这些飞行员 研究旨在为深入评估 吸烟和/或糖尿病损害中性粒细胞介导的机制 防御。

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.