title: Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway.
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.
authors.affiliation: Laboratory for Molecular Nutrition, Faculty of Biotechnology and Food Engineering, Technion, Technion City, Haifa, Israel.
authors.forename: Lyora A
authors.initials: LA
authors.lastname: Cohen
authors.forename: Lucia
authors.initials: L
authors.lastname: Gutierrez
authors.forename: Avital
authors.initials: A
authors.lastname: Weiss
authors.forename: Yael
authors.initials: Y
authors.lastname: Leichtmann-Bardoogo
authors.forename: De-liang
authors.initials: DL
authors.lastname: Zhang
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Crooks
authors.forename: Rachid
authors.initials: R
authors.lastname: Sougrat
authors.forename: Avigail
authors.initials: A
authors.lastname: Morgenstern
authors.forename: Bruno
authors.initials: B
authors.lastname: Galy
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Hentze
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Lazaro
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Rouault
authors.forename: Esther G
authors.initials: EG
authors.lastname: Meyron-Holtz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005293:Ferritins / Q000097:blood*; D006031:Glycosylation; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D021122:Protein Subunits; D055571:Secretory Pathway; D017386:Sequence Homology, Amino Acid
chemical_list: D021122:Protein Subunits; D005293:Ferritins; D007501:Iron