Department of Hematology, Key Laboratory of non-resolving inflammation and cancer of Human Province, The third Xiangya Hospital, Central South University, Changsha, Hunan Province 410000, PR China.
Department of Hematology, Key Laboratory of non-resolving inflammation and cancer of Human Province, The third Xiangya Hospital, Central South University, Changsha, Hunan Province 410000, PR China; Postdoctoral Research Station of Clinical Medicine, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province 410000, PR China.
Clin Immunol. 2019 Aug;205:148-152. doi: 10.1016/j.clim.2018.11.005. Epub 2019 Feb 5.
Ferritin is the major iron storage molecule of vertebrates, which can be detected in serum under numerous conditions, including inflammatory, neurodegenerative, and malignant diseases. Given this character, serum ferritin is frequently used as a biomarker in clinical settings. How the ferritin secreted to the serum has attracted much attention. Although some studies have found ferritin was mediated via the endoplasmic reticulum (ER)-Golgi secretion pathway or secretory lysosomes trafficking pathway under normal conditions, the secretion pathway of ferritin under pathological conditions, especially in sepsis is not very clear. In this report, we adopt a murine sepsis model to study the secretion pathway of ferritin in sepsis. We demonstrated caspase-11-GSDMD pathway and associated pyroptosis are required for secretion of ferritin in vitro and in vivo in sepsis. Moreover, our work connects pyroptosis to serum ferritin secretion and suggests a passive release process of ferritin, enhancing our understanding of the mechanism of ferritin secretion.
铁蛋白是脊椎动物的主要铁储存分子，在许多情况下都可以在血清中检测到，包括炎症、神经退行性和恶性疾病。鉴于这一特点，血清铁蛋白经常被用作临床环境中的生物标志物。铁蛋白如何分泌到血清中引起了广泛关注。尽管一些研究发现铁蛋白在正常条件下是通过内质网（ER）-高尔基体分泌途径或分泌溶酶体运输途径介导的，但在病理条件下，特别是在脓毒症中，铁蛋白的分泌途径还不是很清楚。在本报告中，我们采用小鼠脓毒症模型来研究脓毒症中铁蛋白的分泌途径。我们证明了 caspase-11-GSDMD 途径和相关的细胞焦亡在脓毒症中体外和体内铁蛋白的分泌是必需的。此外，我们的工作将细胞焦亡与血清铁蛋白分泌联系起来，并提示了铁蛋白的一种被动释放过程，从而加深了我们对铁蛋白分泌机制的理解。
