TRANSLOCATING BACTERIA--ROLE IN SURGERY AND TRAUMA

描述：工作假设是，在改变的情况下 肠道通透性，包括失血性休克和 缺血再灌注损伤时，有暴露于 肠细胞的侧面。这进而导致细胞旁 正常非侵袭性的黏附(通过黏附分子)和侵袭 肠道菌群。她的设计模式结合了一种有条理和有逻辑的 利用细胞培养的体外技术的方法(Caco-2和 HT-29细胞)，然后将结果应用于体内模型小鼠。 最初，申请者将试图澄清 肠细胞黏附分子(E-AM)、细菌黏附、 内化和细胞内存活，然后研究 医源性上皮通透性改变对E-AM的影响 表达和细菌与肠道细胞的相互作用。最后她会的 试图阐明E-AM、上皮通透性、 中性粒细胞迁移和细菌-肠道细胞相互作用。粘附性 分子(AM)被认为在细菌-肠道细胞中起主要作用 互动。AM的三个家族对此特别感兴趣 关注：ICAM-1(调节中性粒细胞迁移和降低上皮屏障 功能)、E-钙粘附素(细胞内钙依赖和必需的 粘附性)和整合素(位于基底外侧表面和触发器上 内部化)。威尔斯博士将展示绑定模式，空间 单抗与AM的关系及对AM黏附的影响 在培养细胞和体内模型中的内化。下一个她 然后将研究上皮膜改变对 这些结合模式使用双荧光标记，也使用 无论是培养系还是小鼠模型。最后，两者之间的联系 将对肠上皮细胞AM、细菌和迁移的PMN进行研究。

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.