Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway

被引:384
作者
Cohen, Lyora A. [1 ]
Gutierrez, Lucia [2 ]
Weiss, Avital [1 ]
Leichtmann-Bardoogo, Yael [1 ]
Zhang, De-liang [3 ]
Crooks, Daniel R. [3 ]
Sougrat, Rachid [4 ]
Morgenstern, Avigail [1 ]
Galy, Bruno [5 ]
Hentze, Matthias W. [5 ]
Lazaro, Francisco J. [2 ]
Rouault, Tracey A. [3 ]
Meyron-Holtz, Esther G. [1 ]
机构
[1] Technion Israel Inst Technol, Fac Biotechnol & Food Engn, Lab Mol Nutr, IL-32000 Technion, Haifa, Israel
[2] Univ Zaragoza, Dept Ciencia & Tecnol Mat & Fluidos, Zaragoza, Spain
[3] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, NIH, Bethesda, MD USA
[4] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA
[5] European Mol Biol Lab, Heidelberg, Germany
关键词
HUMAN ERYTHROID PRECURSORS; TRANSFERRIN IRON DELIVERY; ENDOPLASMIC-RETICULUM; REGULATORY PROTEIN-2; DIAGNOSTIC-VALUE; CONCANAVALIN-A; H-FERRITIN; METABOLISM; CELLS; RECEPTOR;
D O I
10.1182/blood-2009-11-253815
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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)
引用
收藏
页码:1574 / 1584
页数:11
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