Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway
Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway
复制标题
DOI：
10.1182/blood-2009-11-253815
复制
发表时间：
2010-09-02
期刊：
影响因子：
20.3
通讯作者：
Meyron-Holtz, Esther G.
中科院分区：
文献类型：
--
作者：
Cohen, Lyora A.;Gutierrez, Lucia;Meyron-Holtz, Esther G.
血清铁蛋白浓度是一项广泛用于贫血鉴别诊断的临床指标。其水平随着组织铁储备的升高和炎症而增加，但对血清铁蛋白的细胞来源及其亚基组成、铁负荷程度和糖基化的研究引起了相互矛盾的结果。为了进一步了解血清铁蛋白，我们使用传统和现代的方法来表征小鼠血清铁蛋白。我们发现，脾巨噬细胞和肾近端小管细胞是血清铁蛋白的可能的细胞来源，血清铁蛋白是由细胞分泌的，而不是从受损细胞的胞质泄漏的产品。小鼠血清铁蛋白主要由L-亚基组成，而它含有很少的H-亚基并且铁含量低。血清铁蛋白的L-亚基经常在C-末端被截短，产生先前在溶酶体铁蛋白中观察到的特征性17-kD带。考虑到小鼠血清铁蛋白没有可检测的糖基化，我们提出小鼠血清铁蛋白是通过非经典的溶酶体分泌途径分泌的。（血。2010; 116（9）：1574-1584）
The serum ferritin concentration is a clinical parameter measured widely for the differential diagnosis of anemia. Its levels increase with elevations of tissue iron stores and with inflammation, but studies on cellular sources of serum ferritin as well as its subunit composition, degree of iron loading and glycosylation have given rise to conflicting results. To gain further understanding of serum ferritin, we have used traditional and modern methodologies to characterize mouse serum ferritin. We find that both splenic macrophages and proximal tubule cells of the kidney are possible cellular sources for serum ferritin and that serum ferritin is secreted by cells rather than being the product of a cytosolic leak from damaged cells. Mouse serum ferritin is composed mostly of L-subunits, whereas it contains few H-subunits and iron content is low. L-subunits of serum ferritin are frequently truncated at the C-terminus, giving rise to a characteristic 17-kD band that has been previously observed in lysosomal ferritin. Taken together with the fact that mouse serum ferritin is not detectably glycosylated, we propose that mouse serum ferritin is secreted through the nonclassical lysosomal secretory pathway. (Blood. 2010; 116(9):1574-1584)