Iron related mechanisms in immune cell function

铁在生物体内有不同的功能。一方面，它是所有细胞所必需的不可替代的微量元素。另一方面，游离铁是有毒的，可能会破坏细胞。这种复杂的相互作用是特别有趣的，例如在免疫细胞功能。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，需要更好地了解铁及其螯合剂在基本细胞水平上的隔离作用。螯合伙伴公司（CP），我们的工业合作伙伴，已经开发了一系列新的铁螯合剂。这些高特异性铁清除物质的可用性使得首次研究铁在体外细胞途径中的不同作用成为可能。这类研究还需要适当的全动物实验来证实铁在整个生物体中的相关机制。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在炎症和感染中的不同作用。炎症模型（无菌无感染诱导剂，如脂多糖）的研究重点是研究铁相关过程，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菌群引起的多微生物感染模型（腹膜炎引起的败血症）进行比较，在这里，我们将试图阐明在潜在炎症过程之上的微生物炎症信号和对感染的反应。* * * * * *

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. ******