ENVIRONMENTAL REGULATION OF NEUTROPHIL EXTRAVASATION

中性粒细胞从外周血管系统向外周血管的迁移 牙周组织是宿主保护的重要组成部分 对微生物菌斑堆积的反应。中性粒细胞外渗 受感染部位是由局部释放的炎性物质介导的 分子，内皮细胞和中性粒细胞表达黏附分子 细胞群，以及作为反应的中性粒细胞的刺激迁移 趋化蛋白和脂类的释放。自更改以来 中性粒细胞功能与牙周疾病的发病有关 疾病，总体来说。这项提议的目标是开发一种智能 研究环境因素对细胞毒性影响的体外模型 中性粒细胞渗出部位。牙周炎和TO 描述发生的任何有害的后遗症。这些目标将是 具体目标如下：(1)建立体外培养体系 人血管壁组织培养体系的构建 小室系统，将允许研究粘附性和生理学 中性粒细胞通过内皮、基底膜和类型的迁移 I型胶原对趋化蛋白和脂类的反应。(二)学习 中性粒细胞对黏附分子表达的调节作用 内皮细胞对肿瘤坏死因子-1存在下的趋化刺激的反应 A、IL-1、内毒素、牙龈卟啉单胞菌或放线杆菌 伴生放线菌；分析将使用血液的原位标记 单细胞悬液的管壁构建及流式细胞仪分析。(3) 研究黏附分子表达改变对血管内皮细胞生长的影响 中性粒细胞跨内皮细胞迁移及其病理改变 由于中性粒细胞的改变而产生的内皮细胞- 内皮细胞相互作用。这些研究将提供重要的 关于特定炎症对环境影响的信息 中性粒细胞与内皮细胞相互作用的分子。在……里面 此外，这种体外构建的发展将提供一种 为进一步研究寄主和细菌的影响提供了极好的模型 炎症、分子对牙周组织中白细胞渗出的影响 疾病。

The migration of neutrophils from the peripheral vasculature to the periodontal tissues is an essential component of the host's protective response to the accumulation of microbial plaque. Neutrophil extravasation to infected sites is mediated by the local release of inflammatory molecules, expression of adhesion molecules by endothelial and neutrophil cell populations, and the stimulated migration of neutrophils in response to the release of chemotactic proteins and lipids. Since altered neutrophil function has been implicated in the pathogenesis of periodontal disease, the overall. objectives of this proposal are to develop an in vitro model for studying the influence of environmental factors on neutrophil extravasation at sites of. periodontal inflammation and to characterize any deleterious sequelae that occur. These objectives will be addressed by the following specific aims: (1) To establish an in vitro tissue culture construct of the human blood vessel wall using a dual chamber system, that will allow the study of the adherence and physiologic migration of neutrophils through endothelium, basement membrane and type I collagen in response to chemotactic proteins and lipids. (2) To study the modulation of adhesiOn molecule expression by neutrophils and endothelium in response to chemotactic stimulation in the presence of TNF- a, IL-1, LPS, Porphyromonas gingivalis or Actinobacillus actinomycetemcomitans; analysis will use in situ labeling of the blood vessel wall construct and FACS analysis of single cell suspensions. (3) To characterize the effects of altered adhesion molecule expression on transendothelial migration of neutrophils and the pathologic changes in endothelial cells that occur as a result of the altered neutrophil- endothelial cell interaction. These studies will provide important information on the environmental effects of specific inflammatory molecules on the interaction of neutrophils and endothelial cells. In addition, the development of this in vitro construct will provide an excellent model for future studies of the effects of host and bacterial inflammatory,molecules on leukocyte extravasation in the periodontal diseases.