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

Lyora A. Cohen, Lucia Gutierrez, Avital Weiss, Yael Leichtmann-Bardoogo, De Liang Zhang, Daniel R. Crooks, Rachid Sougrat, Avigail Morgenstern, Bruno Galy, Matthias W. Hentze, Francisco J. Lazaro, Tracey A. Rouault, Esther G. Meyron-Holtz

Research output: Contribution to journalArticlepeer-review

249 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1574-1584
Number of pages11
JournalBlood
Volume116
Issue number9
DOIs
StatePublished - Sep 2 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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