PMID- 26441243
OWN - NLM
STAT- MEDLINE
DCOM- 20160601
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 10
DP  - 2015
TI  - H-Ferritin Is Preferentially Incorporated by Human Erythroid Cells through 
      Transferrin Receptor 1 in a Threshold-Dependent Manner.
PG  - e0139915
LID - 10.1371/journal.pone.0139915 [doi]
LID - e0139915
AB  - Ferritin is an iron-storage protein composed of different ratios of 24 light (L) 
      and heavy (H) subunits. The serum level of ferritin is a clinical marker of the 
      body's iron level. Transferrin receptor (TFR)1 is the receptor not only for 
      transferrin but also for H-ferritin, but how it binds two different ligands and 
      the blood cell types that preferentially incorporate H-ferritin remain unknown. 
      To address these questions, we investigated hematopoietic cell-specific ferritin 
      uptake by flow cytometry. Alexa Fluor 488-labeled H-ferritin was preferentially 
      incorporated by erythroid cells among various hematopoietic cell lines examined, 
      and was almost exclusively incorporated by bone marrow erythroblasts among human 
      primary hematopoietic cells of various lineages. H-ferritin uptake by erythroid 
      cells was strongly inhibited by unlabeled H-ferritin but was only partially 
      inhibited by a large excess of holo-transferrin. On the other hand, 
      internalization of labeled holo-transferrin by these cells was not inhibited by 
      H-ferritin. Chinese hamster ovary cells lacking functional endogenous TFR1 but 
      expressing human TFR1 with a mutated RGD sequence, which is required for 
      transferrin binding, efficiently incorporated H-ferritin, indicating that TFR1 
      has distinct binding sites for H-ferritin and holo-transferrin. H-ferritin uptake 
      by these cells required a threshold level of cell surface TFR1 expression, 
      whereas there was no threshold for holo-transferrin uptake. The requirement for a 
      threshold level of TFR1 expression can explain why among primary human 
      hematopoietic cells, only erythroblasts efficiently take up H-ferritin.
FAU - Sakamoto, Soichiro
AU  - Sakamoto S
AD  - Department of Hematology and Oncology, Graduate School of Medicine, Kyoto 
      University, Kyoto, Japan; Department of Hematology, Japanese Red Cross Takatsuki 
      Hospital, Takatsuki, Japan.
FAU - Kawabata, Hiroshi
AU  - Kawabata H
AD  - Department of Hematology and Oncology, Graduate School of Medicine, Kyoto 
      University, Kyoto, Japan.
FAU - Masuda, Taro
AU  - Masuda T
AD  - Laboratory of Food Quality Design and Development, Division of Agronomy and 
      Horticultural Science, Graduate School of Agriculture, Kyoto University, Kyoto, 
      Japan.
FAU - Uchiyama, Tatsuki
AU  - Uchiyama T
AD  - Department of Hematology and Oncology, Graduate School of Medicine, Kyoto 
      University, Kyoto, Japan; Department of Hematology and Immunology, Japanese Red 
      Cross Otsu Hospital, Otsu, Japan.
FAU - Mizumoto, Chisaki
AU  - Mizumoto C
AD  - Department of Hematology and Immunology, Japanese Red Cross Otsu Hospital, Otsu, 
      Japan.
FAU - Ohmori, Katsuyuki
AU  - Ohmori K
AD  - Department of Clinical Laboratory, Kyoto University Hospital, Kyoto, Japan.
FAU - Koeffler, H Phillip
AU  - Koeffler HP
AD  - Division of Hematology and Oncology, Cedars-Sinai Medical Center, University of 
      California Los Angeles, School of Medicine, Los Angeles, California, United 
      States of America; National University of Singapore, Singapore, Singapore.
FAU - Kadowaki, Norimitsu
AU  - Kadowaki N
AD  - Division of Endocrinology and Metabolism, Hematology, Rheumatology and 
      Respiratory Medicine, Department of Internal Medicine, Graduate School of 
      Medicine, Kagawa University, Takamatsu, Japan.
FAU - Takaori-Kondo, Akifumi
AU  - Takaori-Kondo A
AD  - Department of Hematology and Oncology, Graduate School of Medicine, Kyoto 
      University, Kyoto, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151006
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, CD)
RN  - 0 (CD71 antigen)
RN  - 0 (Receptors, Transferrin)
RN  - 9007-73-2 (Ferritins)
RN  - 9013-31-4 (Apoferritins)
SB  - IM
MH  - Animals
MH  - Antigens, CD/*metabolism
MH  - Apoferritins/*metabolism
MH  - Biological Transport
MH  - CHO Cells
MH  - Cell Line, Tumor
MH  - Cell Membrane/metabolism
MH  - Cricetinae
MH  - Cricetulus
MH  - Erythroid Cells/*metabolism
MH  - Ferritins/metabolism
MH  - Humans
MH  - Receptors, Transferrin/*metabolism
PMC - PMC4595017
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/10/07 06:00
MHDA- 2016/06/02 06:00
PMCR- 2015/10/06
CRDT- 2015/10/07 06:00
PHST- 2015/06/10 00:00 [received]
PHST- 2015/09/19 00:00 [accepted]
PHST- 2015/10/07 06:00 [entrez]
PHST- 2015/10/07 06:00 [pubmed]
PHST- 2016/06/02 06:00 [medline]
PHST- 2015/10/06 00:00 [pmc-release]
AID - PONE-D-15-25273 [pii]
AID - 10.1371/journal.pone.0139915 [doi]
PST - epublish
SO  - PLoS One. 2015 Oct 6;10(10):e0139915. doi: 10.1371/journal.pone.0139915. 
      eCollection 2015.