TRANSLOCATING BACTERIA--ROLE IN SURGERY AND TRAUMA

描述：工作假设是，在改变的情况下， 肠通透性，包括失血性休克， 缺血再灌注损伤时， 肠上皮细胞的侧面。 这反过来又导致细胞旁 粘附（通过粘附分子）和侵袭正常非侵入性 肠道植物群。 她的设计模型结合了一个有组织的和逻辑的 利用细胞培养物的体外技术（Caco-2和 HT-29细胞），然后将结果应用于体内模型，小鼠。 首先，申请人将试图澄清 肠细胞粘附分子（E-AM），细菌粘附， 内化和细胞内存活，然后研究 医源性改变的上皮通透性对E-AM的影响 表达和细菌-肠细胞相互作用。 最后她会 试图阐明E-AM，上皮通透性， 中性粒细胞迁移和细菌-肠上皮细胞相互作用。 粘附 分子（AM）被认为在细菌-肠上皮细胞中起主要作用 互动 AM的三个家族对此特别感兴趣 关于：ICAM-1（调节PMN迁移并降低上皮屏障 功能）、E-钙粘蛋白（细胞间钙依赖性和必需的 粘附）和整合素（位于基底外侧表面并触发 内化）。 威尔斯博士将展示结合模式，空间 的关系，以及抗AM单克隆抗体（mAb）对粘附和 在培养的细胞和体内模型中的内化。 接下来她 然后将研究改变的上皮细胞膜对 这些结合模式使用双荧光染料标记，也使用 培养系和小鼠模型。 最后， 将研究肠上皮细胞AM、细菌和迁移的PMN。

DESCRIPTION: The working hypothesis is that in situations of altered intestinal permeability, which would include hemorrhagic shock and ischemia-reperfusion injury, there is an increased exposure of the lateral surface of the enterocyte. This in turn leads to paracellular adherence (via adhesion molecules) and invasion of normally non-invasive enteric flora. Her design model incorporates an organized and logical approach that utilizes in vitro techniques of cell cultures (Caco-2 and HT-29 cells) and then applies the results in an in vivo model, the mouse. Initially the applicant will attempt to clarify the relationship between enterocyte adhesion molecules (E-AM), bacterial adherence, internalization and intracellular survival, and then investigate the effects of an iatrogenically altered epithelial permeability on E-AM expression and bacteria-enterocyte interactions. Finally she will attempt to clarify the association between E-AM, epithelial permeability, PMN transmigration and bacteria-enterocyte interaction. Adhesion molecules (AM) are felt to play a major role in bacteria-enterocyte interaction. Three families of AM are specifically interesting in this regard: ICAM-1 (modulates PMN migration and decreases epithelial barrier function), E-cadherin (calcium dependent and essential in cell-cell adhesion), and integrins (are located on basolateral surfaces and trigger internalization). Dr. Wells will show the binding pattern, spatial relationship, and effect of monoclonal Ab (mAb) to AM on adherence and internalization in the cultured cells and in the in vivo model. Next she will then investigate the effects of an altered epithelial membrane on these binding patterns using double fluorochrome labeling, also using both the culture line and mouse model. Finally the association between the enterocyte AM, bacteria, and the migrating PMN will be investigated.