Rump Katharina, Adamzik Michael
Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum-Langendreer, Ruhr-Universität Bochum, In der Schornau 23-25, 45882 Bochum, Germany.
Cell Biosci. 2018 Feb 9;8:10. doi: 10.1186/s13578-018-0211-9. eCollection 2018.
Sepsis is a common cause of death in intensive care units worldwide. Due to the high complexity of this immunological syndrome development of novel therapeutic strategies is urgent. Promising drug targets or biomarkers may depict aquaporins (AQPs) as they regulate crucial key mechanisms of sepsis.
Here we report on base of the current literature that several AQPs are involved in different physiological processes of sepsis. In immune system mainly AQPs 3, 5 and 9 seem to be important, as they regulate the migration of different immune cells. Several studies showed that AQP3 is essential for T cell function and macrophage migration and that AQP5 and AQP9 regulate neutrophil cell migration and impact sepsis survival. Additionally, to the function in immune system AQPs 1 and 5 play a role in sepsis induced lung injury and their downregulation after inflammatory stimuli impair lung injury. By contrast, AQP4 expression is up-regulated during brain inflammation and aggravates brain edema in sepsis. In kidney AQP2 expression is downregulated during sepsis and can cause renal failure. Some studies also suggest a role of AQP1 in cardiac function.
In conclusion, AQPs are involved in many physiological dysfunctions in sepsis and their expressions are differently regulated. Additional research on the regulatory mechanisms of aquaporins may identify potential therapeutic targets.
脓毒症是全球重症监护病房常见的死亡原因。由于这种免疫综合征的高度复杂性,开发新的治疗策略迫在眉睫。有前景的药物靶点或生物标志物可能是水通道蛋白(AQP),因为它们调节脓毒症的关键机制。
在此,我们基于当前文献报道,几种水通道蛋白参与了脓毒症的不同生理过程。在免疫系统中,主要是水通道蛋白3、5和9似乎很重要,因为它们调节不同免疫细胞的迁移。多项研究表明,水通道蛋白3对T细胞功能和巨噬细胞迁移至关重要,水通道蛋白5和水通道蛋白9调节中性粒细胞迁移并影响脓毒症的存活率。此外,除了在免疫系统中的功能外,水通道蛋白1和5在脓毒症诱导的肺损伤中起作用,炎症刺激后它们的下调会加重肺损伤。相比之下,在脑部炎症期间水通道蛋白4表达上调,并加重脓毒症中的脑水肿。在肾脏中,脓毒症期间水通道蛋白2表达下调,可导致肾衰竭。一些研究还表明水通道蛋白1在心脏功能中起作用。
总之,水通道蛋白参与了脓毒症中的许多生理功能障碍,并且它们的表达受到不同的调节。对水通道蛋白调节机制的进一步研究可能会确定潜在的治疗靶点。