中性多形核白细胞在牙周炎中的作用及其分子机制

中性多形核白细胞(PMN)是宿主抵抗牙周致病菌侵袭的重要吞噬细胞,炎症反应中PMN在趋化因子的作用下,通过其表面与内皮细胞粘附分子间的相互作用移出血管进入组织,与牙周炎的临床表现紧密相关,但对各型牙周炎患者PMN的研究显示PMN异常可能不是唯一的病理机制,全身因素似更为重要。     

纤维蛋白原对牙周炎病人中性多形核白细胞分泌IL-1β和IL-8水平的影响

目的:分析重度牙周炎病人中性多形核白细胞(PMN)分泌功能和急性期纤维蛋白原对其影响.方法:以梯度密度离心法分离牙周健康和重度牙周炎者外周血PMN,以纤维蛋白原和趋化肽fMLP刺激PMN,ELISA法测定其分泌IL-1β和IL-8的水平.结果:受纤维蛋白原或fMLP刺激,重度牙周炎者PMN分泌IL-1β和IL-8的水平高于牙周健康者(P<0.05);不论牙周状态,与纤维蛋白原作用后,PMN分泌IL-1β和IL-8的水平显著高于对照组及fMLP刺激组(P<0.05).结论:重度牙周炎病人PMN具有"过度炎症反应性"特征,纤维蛋白原与PMN的作用可促进炎症反应,加重牙周破坏.     

糖尿病并发牙周炎患者的嗜中性粒细胞（PMN）功能的研究

不同类型牙周病与PMN功能之间的关系,近几年来国外有许多研究。牙周病时PMN从牙龈组织的血管中游出到结合上皮和牙周袋内,吞噬、杀死细菌,起着第一道防线的作用。糖尿病病人机体代谢紊乱,可能影响PMN的细胞代谢,导致PMN的功能改变。本研究检测了以下四组受试者PMN趋化、吞噬功能。第1组:糖尿病并发牙周炎组,第2组:糖尿病牙周组织健康组,第3组:成年人牙周炎组,第4组:正常人组。结果发现糖尿病并发牙周炎患者的PMN趋化、吞噬功能明显低于糖尿病牙周组织健康组、一般成年人的牙周炎组和正常人组。而后三组之间比较无显著差别。这一研究结果表明:PMN趋化、吞噬功能低下,在糖尿病并发牙周炎的病因学方面,起着非常重要的作用。     

尼古丁对牙周炎相关细胞影响的研究

牙周炎是以菌斑微生物为始动因子,宿主和其它因素共同作用导致的牙周支持组织广泛破坏的疾病。牙周膜成纤维细胞、牙龈成纤维细胞、成/破骨细胞对维持牙周组织的健康至关重要,而上述细胞功能的异常都可能导致牙周炎的发生。此外,中性粒细胞等免疫细胞也在牙周炎的发生发展中也扮演着重要的角色。     

局限型青少年牙周炎中性多形核白细胞功能缺陷机制

70％～75％局限型青少年牙周炎(LJP)患者存在中性多形核白细胞(PMN)功能缺陷,其影响因素众说纷纭。本文就其固有功能异常、机体遗传因素影响、细胞因子影响及特异性病原菌伴放线放线杆菌作用4方面进行综述,旨在阐明其发生机制及在LJP发病中的作用。     

白细胞介素8及牙周主要致病菌对其的调节作用

牙周炎是一种感染性疾病 ,它的特点是细菌感染造成牙周附着丧失和牙槽骨的吸收。宿主对Ｇ-厌氧菌及其产物脂多糖 (ＬＰＳ)的反应 ,是牙周炎发生发展的重要的决定性因素。许多方面的证据表明 ,中性粒细胞 (ＰＭＮ)在牙周炎中保持宿主和细菌间的平衡起关键性作用。宿主对细菌的有     

青少年牙周炎患者中性白细胞功能的研究进展

牙周病是局部细菌及其代谢产物与宿主反应相互作用的结果,它的基本病理改变是炎症,中性白细胞是机体抗感染中重要反应细胞,它在牙周疾病与健康中的作用,已受到不少学者的重视,特别是近年来发现青少年牙周炎患者有中性白细胞功能障碍存在,引起了众多研究者的兴趣,青少年牙周炎已成为研究中性白细胞功能与细菌感染相互关系的极好模型。本文就国外对青少年牙周炎患者中性血细胞功能研究的状况作一综述,并提出今后这方面的研究方向。一、青少年牙周炎患者中性白细胞功能特点近二十年来,局部细菌及其代谢产物在牙周病发生发展中的作用已变得非常清楚。另一方面,个体的敏感性即宿主反应又在很大程度上影响牙周病变的发生发展,青少年牙周炎发生年龄早,病     

慢性牙周炎全身相关危险因素

慢性牙周炎是由口腔混合菌群引起的慢性感染性疾病,能够造成牙周支持组织破坏,最终导致牙齿缺失、影响咀嚼功能。多种复杂因素能够影响牙周疾病的发生、发展和预后,其中全身因素在影响疾病发展变化和指导临床治疗工作中具有重要作用。本文将对慢性牙周炎全身相关危险因素进行简要阐述。     

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目的探讨中性多形核白细胞(PMN)在重度慢性牙周炎发病机制中的作用。方法2005年11月至2006年3月,于四川大学华西口腔医学院收集牙周健康者和重度慢性牙周炎患者各4人作为研究对象,以梯度密度离心法分离外周血PMN,并与趋化肽fMLP作用,酶联免疫吸附试验(ELISA)法测定其分泌白细胞介素(IL)-1β和IL-8的质量浓度。结果重度慢性牙周炎患者PMN分泌IL-1β和IL-8的质量浓度高于牙周健康者(P<0.05),且fMLP对PMN的刺激作用具有时间依赖性,随作用时间延长,PMN分泌IL-1β和IL-8的质量浓度升高(P<0.01)。结论重度慢性牙周炎患者PMN具有"过度炎症反应性"特征,可分泌高质量浓度的IL-1β和IL-8,在牙周炎发病机制中具有一定作用。     

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慢性牙周炎是由口腔混合茵群引起的慢性感染性疾病,能够造成牙周支持组织破坏,最终导致牙齿缺失、影响咀嚼功能。多种复杂因素能够影响牙周疾病的发生、发展和预后,其中全身因素在影响疾病发展变化和指导临床治疗工作中具有重要作用。本文将对慢性牙周炎全身相关危险因素进行简要阐述。     

Congenital neutrophil defects and periodontal diseases

An alteration of the immune system function is one of the main factors involved in the development of periodontal disease. Polymorpho-nuclear neutrophil leukocytes (PMN) play a crucial role in the cell-mediated immune response against bacterial challenge. The mechanism of neutralization of pathogen microorganisms by PMNs involves many different steps: adhesion to capillary endothelium in the inflamed region, trans-endothelial migration, chemotaxis, phagocytosis and, ultimately, bacterial killing by oxidative and non-oxidative mechanisms. A defect in one of these steps leads to altered neutrophil function and, consequently, to a higher host susceptibility to periodontal tissue infection. The main intrinsic neutrophil diseases such as neutropenia, leukocyte adhesion deficiency (LAD-1), Chediak-Higashi syndrome, Papillon-Lefèvre syndrome, chronic granulomatous disease (CGD), are often related to severe and early-onset forms of periodontitis, as described by many evidences in the literature. Therefore PMN dysfunctions, both intrinsic and extrinsic, represent an important risk factor for periodontal disease. Studies on the basic molecular mechanisms of such dysfunctions, also in terms of genetic polymorphisms, recently allowed to identify some specific markers related to a higher susceptibility to the development of disease. Many researches have yet to be performed aiming to gain insight on the dynamics of PMN activation and interaction with other cells, in order to improve and modulate neutrophil function and to develop specific approaches for care and prevention of periodontal diseases.     

Gingival crevice neutrophil function in periodontal lesions

Polymorphonuclear neutrophils (PMN) may play an important role in protection of the host from pathogenic microorganisms associated with periodontal tissue destruction. The purpose of the present study was to test the hypothesis that unusually severe periodontitis may be associated with defective PMN function at the local disease site. The patients studied included young patients with rapidly progressive periodontitis (including juvenile periodontitis), age-matched patients with gingivitis, and older patients with chronic periodontitis. Gingival crevice (GC) PMN were collected from 10 lesions of each patient by a crevicular washing technique. The number and viability of GC PMN recovered were determined. Their phagocytic capacity was assayed in vitro as a percentage of cells capable of engulfing latex particles. No differences were observed between the periodontitis groups in the number or viability of GC PMN recovered. A statistically significant reduction in mean phagocytic capacity was observed in PMN recovered from lesions of rapidly progressive periodontitis when compared with lesions of chronic periodontitis (12.9 ± 2.1 % vs. 83.7 ± 4.8 %). GC PMNs recovered from non-diseased sites of patients with localized juvenile periodontitis did not show this decreased function. These results suggest that locally diminished PMN function in rapidly progressive and juvenile periodontitis is associated with the environment of these lesions.     

Ex vivo studies of polymorphonuclear neutrophils from patients with early-onset forms of periodontitis (I).

Abstract The polymorphonuclear neutrophil (PMN) appears lo be an important cell in the protection of the host from pathogenic periodontal microorganisms and, despite some reports to the contrary, it is generally assumed that early-onset forms of periodontal disease including both juvenile and rapidly progressing periodontitis are associated with a defect in PMN chemotactic behaviour. The purpose of the present study was to examine the peripheral PMN chemotactic behaviour, using the under agarose method, in 4 groups, namely healthy periodontium group (n= 7), gingivitis group (n= 8), early-onset periodontitis group (n= 17) and adult periodontitis group (n= 8). PMN from early-onset periodontitis patients showed normal random and chemotactic locomotory behaviour when compared with those of PMN from subjects of the other groups. No statistically significant difference could be found among the 4 studied groups, with regard to spontaneous and oriented migration.     

Periodontal disease in juvenile and adult diabetic patients: a review of the literature

Epidemiologic studies have suggested that the severity of periodontitis is greater in juvenile and adult onset diabetes. In juvenile diabetic patients, the periodontal disease seems to be initiated around puberty and progresses by age. Reviewing the medical literature indicates a similar age of onset for known systemic complications resulting from diabetes. Angiopathy, abnormal collagen metabolism, abnormal PMN function, and altered sulcular microbial flora have been found to be closely associated with the severity of periodontitis in diabetic patients. The association between abnormal neutrophil function and severity of periodontal disease in diabetic patients provides an opportunity for examining the role of neutrophil in periodontal disease. Future investigation in the function of sulcular PMN may shed light on the complex mechanism of periodontal disease.     

Neutrophil migration, oxidative metabolism and adhesion in early onset periodontitis

The aim of this study was to evaluate neutrophil function in patients suffering from the generalized form of early onset periodontitis (EOP). We investigated neutrophil migration in vivo and neutrophil superoxide production and adhesion in response to a variety of compounds; neutrophils were isolated both from blood and a skin experimental exudate of 15 patients with EOP and of 15 sex- and age-matched normal control subjects. No difference was found in neutrophil migration in vivo (71.2+/-16.4x10(6) and 68.8+/-10.7x10(6) PMN/cm2/24 h in patients affected by early onset periodontitis and normal subjects respectively) and in adhesion. The superoxide production in response to STZ and PMA was similar between the 2 groups, while superoxide production in response to fMLP was markedly lower in patients than in control subjects both in circulating neutrophils (5.6+/-2.2 versus 10.4+/-2.3 nmoles O2-/10(6) cells, p<0.0001) and in exudate neutrophils (16.3+/-4.3 versus 22.3+/-4.7 nmoles O2-/10(6) cells, p<0.005). In general, neutrophil function in patients suffering from early onset periodontitis does not differ from control subjects, suggesting that the overall defence function of these cells is normal. The only parameter that we have found to be different between the 2 groups is the low superoxide production after fMLP stimulation. The stimulus- and function-specificity of this defect in neutrophils from patients indicates the existence of a dysregulation of the signal transduction pathway distal to fMLP receptor and proximal to NADPH oxidase activation.     

Chemiluminescence in the assessment of polymorphonuclear leukocyte function in chronic inflammatory periodontal disease

Polymorphonuclear neutrophils (PMN's) constitute the primary host resistance factor against infection. They are prominent cells in both the gingival tissue and gingival sulcus in most forms of periodontal disease. Although defective PMN function has been implicated in the pathogenesis of localized juvenile periodontitis (LJP) and rapidly progressive periodontitis (RPP), this may not necessarily be the case in adult periodontitis (AP). A number of studies have failed to detect PMN dysfunction in AP. However, it may be that in this form of chronic inflammatory periodontal disease (CIPD) the defects in peripheral blood PMN function are subtle and the methods used may lack the necessary sensitivity. Chemiluminescence (CL) is the light energy produced by the PMN during its interaction with bacteria or other particles and has been demonstrated to correlate well with antibacterial integrity. Measurement of CL produced by phagocytically challenged PMN's may provide a very sensitive assay of the functional ability of these cells, and, hence, may be useful in assessing PMN activity in CIPD. Recent studies using PMN's obtained from periodontal diseased patients challenged with the periodontopathic organism Fusobacterium nucleatum have revealed an elevated CL response compared to non-diseased controls. These results are reviewed and areas for future research discussed.     

Chemiluminescence in the assessment of polymorphonuclear leukocyte function in chronic inflammatory periodontal disease

Polymorphonuclear neutrophils (PMN's) constitute the primary host resistance factor against infection. They are prominent cells in both the gingival tissue and gingival sulcus in most forms of periodontal disease. Although defective PMN function has been implicated in the pathogenesis of localized juvenile periodontitis (UP) and rapidly progressive periodontitis (RPP), this may not necessarily be the case in adult periodontitis (AP). A number of studies have failed to detect PMN dysfunction in AP. However, it may be that in this form of chronic inflammatory periodontal disease (CIPD) the defects in peripheral blood PMN function are subtle and the methods used may lack the necessary sensitivity. Chemiluminescence (CL) is the light energy produced by the PMN during its interaction with bacteria or other particles and has been demonstrated to correlate well with antibacterial integrity. Measurement of CL produced by phagocytically challenged PMN's may provide a very sensitive assay of the functional ability of these cells, and, hence, may be useful in assessing PMN activity in CIPD. Recent studies using PMN's obtained from periodontal diseased patients challenged with the periodontopathic organism Fusobacterium nucleaium have revealed an elevated CL response compared to non-diseased controls. These results are reviewed and areas for future research discussed.     

快速进展性牙周炎患者的白细胞趋化功能

目的了解我国快速进展性牙周炎患者的外周血中性多形核白细胞是否存在趋化功能异常。方法选择细菌源性的趋化肽和宿主源性的趋化因子（白细胞介素８）作为趋化剂，采用微孔滤膜法（改良的ＢｏｙｄｅｎＣｈａｍｂｅｒ法）检测１６例快速进展性牙周炎患者的外周血中性多形核白细胞的趋化功能，并与１４名年龄相当的健康个体进行对照。结果快速进展性牙周炎患者的外周血中性多形核白细胞对细菌源性的趋化肽和白细胞介素８的趋化反应与健康组差异无显著性。结论中性多形核白细胞趋化功能的异常可能并不是快速进展性牙周炎的主要易感因素。     

New developments in neutrophil biology and periodontitis

Neutrophils have been historically associated with antimicrobial functions in acute infections but are now appreciated as functionally versatile cells with critical roles in chronic inflammation. Recent advances in neutrophil biology have contributed to a better understanding of periodontal disease pathogenesis and, reciprocally, the study of periodontitis has led to important insights into neutrophil regulation and function. Here, the contributions by our group to this field through interdisciplinary collaboration are discussed. The study of leukocyte adhesion deficiency-associated periodontitis has revealed that the connection of neutrophils with destructive inflammation may involve mechanisms beyond the typical bystander injury dogma. In this regard, neutrophils are required for important immunomodulatory functions and their absence from the periodontium leads to dysregulated overproduction of interleukin-17, which drives inflammatory bone loss. We have also discovered that both the production of neutrophils in the bone marrow and their recruitment to peripheral tissues, including the periodontium, are homeostatically regulated by a secreted protein designated developmental endothelial locus-1. However, developmental endothelial locus-1 expression, and hence developmental endothelial locus-1-dependent homeostasis, declines considerably with aging and contributes to an increased susceptibility to periodontitis in old age. Moreover, our work has mechanistically supported the concept that periodontitis is a dysbiotic disease and we have shown that neutrophils become targets of immune subversion by periodontal bacteria in a manner that promotes dysbiosis. The mechanism involves microbial exploitation of key neutrophil receptors (complement C5a receptor-1 and toll-like receptor-2), leading to crosstalk signaling that uncouples neutrophil-mediated killing (which is impaired) from neutrophil-induced inflammation (which is enhanced). These studies have collectively established new mechanisms governing the protective and destructive functions of neutrophils in periodontitis and offered targeted host-modulation approaches for the treatment of periodontal diseases.