Investigation of the function of zinc in the cellular signal transduction of monocytes

锌是免疫系统必需的微量元素。我们的结果表明，在其他功能中，锌离子是单核细胞信号转导的组成部分。在之前的资助期间，我们分析了锌信号在病原诱导信号中的作用。在目前的应用中，我们打算研究锌信号在单核细胞前体分化中的作用。初步数据显示，细胞分化伴随着游离锌的减少，而螯合剂进一步减少细胞内的游离锌会强烈促进单核细胞的分化。我们将研究这些细胞锌稳态的变化如何有助于分化过程，并表征细胞中受锌调控的分子事件。此外，我们将研究锌是否是单核细胞形成的特定触发因素，或者促进共同前体细胞分化为其他类型的细胞，特别是粒细胞。最后，通过研究单核细胞功能的其他参数，我们将分析锌对单核细胞功能的影响，以及锌状态与原代人类造血干细胞向单核细胞分化的生物学相关性。

Zinc is an essential trace element for the immune system. Our results indicate that, among other functions, zinc ions are a component of monocytic signal transduction. During the previous funding period we analyzed the role of zinc signals in pathogeninduced signaling. In the present application we intend to investigate the function of zinc signals for the differentiation of monocytic precursors. Preliminary data show that differentiation is accompanied by a decrease in free zinc and that a further reduction of free intracellular zinc by chelators strongly augments monocytic differentiation. We will investigate how changes in the zinc homeostasis of these cells contribute to the differentiation process and characterize the molecular events in the cell that are regulated by zinc. Furthermore, we will examine if zinc is a specific trigger for monocyte formation, or promotes differentiation of the common precursor cells into other cell types, especially granulocytes, as well. Finally, by investigating additional parameters of monocyte function we will analyze the effects of zinc on the functionality of the monocytes and the biological relevance of the zinc status for monocytic differentiation from primary human haematopoietic stem cells.