Iron related mechanisms in immune cell function

铁在生物体中具有不同的功能。一方面，它是所有细胞所需的不可替代的微量元素。另一方面，游离铁是有毒的，可以参与细胞破坏。这种复杂的相互作用特别令人感兴趣，例如在免疫细胞功能中。铁清除剂（螯合剂）能够调节免疫系统对炎症或感染等触发因素的反应。然而，需要更好地理解铁及其螯合剂在基本细胞水平上起的作用。螯合合作伙伴公司(CP)，我们的工业合作伙伴，开发了一系列新型铁螯合剂。这些高度特异性铁清除物质的可用性使得首次有可能研究铁在体外细胞途径中发挥的不同作用。此类研究还需要适当的整体动物实验来确认完整生物体中的铁相关机制。我们建立了完整的动物模型系统和体内方法来研究铁及其螯合在炎症和感染中的不同作用。炎症模型（来自无菌无感染诱导剂，例如脂多糖）的研究重点是研究铁相关过程，例如活性氧的产生，以及铁去除对免疫细胞功能的影响。这些反应将与由天然肠道植物群（腹膜炎诱导的脓毒症）引起的多微生物感染模型进行比较，在此我们将试图阐明在潜在炎症过程之上的组合微生物炎症信号传导和对感染的反应。******

Iron has different functions in living beings. On one hand it is required as an irreplaceable trace element by all cells. On the other hand, free iron is toxic and can be involved in cellular destruction. This complex interplay is of particular interest for example in immune cell function. Iron scavenging agents (chelators) are able to modulate the response of the immune system to triggers like inflammation or infection. However, a better understanding of the discrete roles that iron and its sequestration by chelators plays at the basic cellular level is needed. Chelation Partners Inc. (CP), our Industrial Partner, has developed a family of novel iron chelators. The availability of those highly-specific iron scavenging substances makes it possible for the first time to investigate the different roles that iron plays in cellular pathways in vitro. Such studies also require appropriate whole animal experiments to confirm the iron-related mechanisms in the complete organism. We have established whole animal model systems and in vivo methods to study the differential roles of iron and its sequestration in both inflammation and infection. The focus of the research in the inflammatory models (from sterile infection-free inducers, e.g. lipopolysaccharide) is the study of iron-related processes, e.g. reactive oxygen species generation, and the impact of iron removal on immune cell function. These responses will be compared to a polymicrobial infection model caused from natural gut flora (peritonitis-induced sepsis) and here we will attempt to elucidate the combined microbial inflammation signaling and response to infection on top of the underlying inflammatory processes. ******