PMID- 25041478
OWN - NLM
STAT- MEDLINE
DCOM- 20150212
LR  - 20211021
IS  - 1537-2995 (Electronic)
IS  - 0041-1132 (Print)
IS  - 0041-1132 (Linking)
VI  - 54
IP  - 12
DP  - 2014 Dec
TI  - Macrophages clear refrigerator storage-damaged red blood cells and subsequently 
      secrete cytokines in vivo, but not in vitro, in a murine model.
PG  - 3186-97
LID - 10.1111/trf.12755 [doi]
AB  - BACKGROUND: In mice, refrigerator-stored red blood cells (RBCs) are cleared by 
      extravascular hemolysis and induce cytokine production. To enhance understanding 
      of this phenomenon, we sought to model it in vitro. STUDY DESIGN AND METHODS: 
      Ingestion of refrigerator-stored murine RBCs and subsequent cytokine production 
      were studied using J774A.1 mouse macrophage cells and primary murine splenic 
      macrophages. Wild-type and Ccl2-GFP reporter mice were used for RBC clearance in 
      vivo. RESULTS: Although J774A.1 cells and primary macrophages preferentially 
      ingested refrigerator-stored RBCs in vitro, compared to freshly isolated RBCs, 
      neither produced increased cytokines after erythrophagocytosis. In contrast, 
      phagocytosis of refrigerator-stored RBCs in vivo induced increases in circulating 
      monocyte chemoattractant protein-1 (MCP-1) and keratinocyte chemoattractant (KC) 
      and correspondingly increased mRNA levels in mouse spleen and liver. In the 
      spleen, these were predominantly expressed by CD11b+ cells. Using Ccl2-GFP 
      reporter mice, the predominant splenic population responsible for MCP-1 mRNA 
      production was tissue-resident macrophages (i.e., CD45+, CD11b+, F4/80+, Ly6c+, 
      and CD11c(low) cells). CONCLUSION: J774A.1 cells and primary macrophages 
      selectively ingested refrigerator-stored RBCs by phagocytosis. Although cytokine 
      expression was not enhanced, this approach could be used to identify the relevant 
      receptor-ligand combination(s). In contrast, cytokine levels increased after 
      phagocytosis of refrigerator-stored RBCs in vivo. These were primarily cleared in 
      the liver and spleen, which demonstrated increased MCP-1 and KC mRNA expression. 
      Finally, in mouse spleen, tissue-resident macrophages were predominantly involved 
      in MCP-1 mRNA production. The differences between cytokine production in vitro 
      and in vivo are not yet well understood.
CI  - (c) 2014 AABB.
FAU - Wojczyk, Boguslaw S
AU  - Wojczyk BS
AD  - Department of Pathology and Cell Biology, Columbia University College of 
      Physicians and Surgeons-New York Presbyterian Hospital, New York, New York.
FAU - Kim, Nina
AU  - Kim N
FAU - Bandyopadhyay, Sheila
AU  - Bandyopadhyay S
FAU - Francis, Richard O
AU  - Francis RO
FAU - Zimring, James C
AU  - Zimring JC
FAU - Hod, Eldad A
AU  - Hod EA
FAU - Spitalnik, Steven L
AU  - Spitalnik SL
LA  - eng
GR  - K08 HL103756/HL/NHLBI NIH HHS/United States
GR  - R01 HL098014/HL/NHLBI NIH HHS/United States
GR  - K08-HL103756/HL/NHLBI NIH HHS/United States
GR  - R01-098014/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140720
PL  - United States
TA  - Transfusion
JT  - Transfusion
JID - 0417360
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Cxcl1 protein, mouse)
SB  - IM
MH  - Animals
MH  - *Blood Preservation
MH  - Cell Line
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chemokine CXCL1/genetics/*metabolism
MH  - *Erythrocyte Transfusion
MH  - *Erythrocytes
MH  - Liver/metabolism
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - *Models, Biological
MH  - *Phagocytosis
MH  - Spleen/metabolism
MH  - Time Factors
PMC - PMC4267962
MID - NIHMS596037
COIS- Disclosure: The authors declare no conflicts of interest relevant to the 
      manuscript submitted to Transfusion.
EDAT- 2014/07/22 06:00
MHDA- 2015/02/13 06:00
PMCR- 2015/12/01
CRDT- 2014/07/22 06:00
PHST- 2013/11/02 00:00 [received]
PHST- 2014/04/22 00:00 [revised]
PHST- 2014/04/24 00:00 [accepted]
PHST- 2014/07/22 06:00 [entrez]
PHST- 2014/07/22 06:00 [pubmed]
PHST- 2015/02/13 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 10.1111/trf.12755 [doi]
PST - ppublish
SO  - Transfusion. 2014 Dec;54(12):3186-97. doi: 10.1111/trf.12755. Epub 2014 Jul 20.