Epithelial wound healing in 3 dimensions

超过95%的感染性物质通过暴露的粘膜表面进入，如 呼吸道、胃肠道和泌尿生殖道。其中包括艾滋病毒、性传播疾病、 许多机会性感染，结核病，许多新出现和再次出现的感染，以及生物 战争/恐怖分子毒剂，如炭疽、鼠疫耶尔森氏菌和天花。大多数粘膜表面都有 由极化的上皮细胞组成的单层，构成了感染性病原体进入的主要屏障。在……里面 本质上，上皮层可以被认为是天然粘膜免疫的最基本的组成部分。 系统。一些病原体通过破坏上皮层来穿过上皮层。其他病原体利用中断 单层，可由继发于炎症、创伤的组织损伤引起，或可能由 单层内细胞死亡或分裂。为了保持它们作为感染屏障的功能，上皮细胞 组织已经发展出有效的伤口愈合机制。伤口愈合是粘膜防御的核心 抗感染。必须尽快恢复上皮屏障，以将机会降至最低 用于传染病病原体的进入。一些感染性病原体，如铜绿假单胞菌，不仅利用 既有伤口，也阻碍伤口愈合过程。我们正在研究上皮伤口的愈合 通过在三维培养的细胞外基质中培养上皮细胞，这会使细胞更多 与活体条件非常相似。在目标1中，我们使用的是人类原发肺泡II型系统。 形成肺泡样囊肿的细胞作为研究急性肺损伤/急性呼吸反应的模型 窘迫综合症。在目标2中，我们使用的是一个分化良好的人体呼吸道的三维系统 以假复层上皮为衬里形成囊泡和小管的细胞系，作为研究呼吸道的模型 对伤害的反应。在目标3中，我们正在研究基质金属蛋白酶和硫酸酯酶(酶)的作用 在我们的三维培养中从硫酸乙酰肝素蛋白多糖中去除6-O-硫酸盐基团 系统。这项工作将与项目2、3和4合作，并得到核心B和C的支持。 大多数感染性病原体是通过内脏的细胞层进入的，比如肺。 对这一细胞层的损伤使病原体更容易进入，我们正在研究细胞层如何 会自我修复的。

Greater than 95% of infectious agents enter through exposed mucosal surfaces, such as the respiratory, gastrointestinal and genitourinary tracts. These include HIV, sexually transmitted diseases, numerous opportunistic infections, TB, many emerging and re-emerging infections, and biological warfare/terrorist agents, such as anthrax, Yersinia pestis and small pox. Most mucosal surfaces are lined by a monolayer of polarized epithelial cells, which forms the principal barrier to entry by infectious agents. In essence, the epithelial layer can be considered the most basic component of the innate mucosal immune system. Some pathogens cross the epithelial layer by disrupting it. Other pathogens exploit disruptions in the monolayer, which can be caused by tissue injury secondary to inflammation, trauma, or may result from cell death or division within the monolayer. To maintain their function as a barrier to infection, epithelial tissues have developed efficient wound healing mechanisms. Wound healing is central to mucosal defense against infection. The epithelial barrier must be restored as quickly as possible, to minimize the opportunity for entry of infectious agents. Some infectious agents, such as Pseudomonas aeruginosa, not only exploit pre-existing wounds, but also impede the wound healing process. We are studying epithelial wound healing by growing epithelial cells in 3 dimensional cultures of extracellular matrix, which causes the cells to more closely resemble in vivo conditions. In Aim 1 we are using a system of human primary lung alveolar type II cells, which form alveolar-like cysts, as a model to study response to acute lung injury/acute respiratory distress syndrome. In Aim 2, we are using a three-dimensional system of a well-differentiated human airway cell line, which forms cysts and tubules lined by pseudostratified epithelium, as a model to study airway response to injury. In Aim 3 we are studying the roles of matrix metalloproteinases and sulfatases (enzymes that remove 6-O-sulfate groups from heparan sulfate proteoglycans) in our three dimensional culture systems. This work will be in collaboration with Projects 2, 3 and 4, and supported by Cores B and C. Most infectious agents enter through the layer of cells that lines internal organs, such as the lung. Injuries to this cell layer makes it much easier for pathogens to enter and we are studying how the cell layer heals itself.