PMID- 25242651
OWN - NLM
STAT- MEDLINE
DCOM- 20150729
LR  - 20230705
IS  - 1878-7568 (Electronic)
IS  - 1742-7061 (Print)
IS  - 1742-7061 (Linking)
VI  - 11
DP  - 2015 Jan
TI  - Loss of monocyte chemoattractant protein-1 alters macrophage polarization and 
      reduces NFkappaB activation in the foreign body response.
PG  - 37-47
LID - S1742-7061(14)00405-X [pii]
LID - 10.1016/j.actbio.2014.09.022 [doi]
AB  - Implantation of biomaterials elicits a foreign body response characterized by 
      fusion of macrophages to form foreign body giant cells and fibrotic 
      encapsulation. Studies of the macrophage polarization involved in this response 
      have suggested that alternative (M2) activation is associated with more favorable 
      outcomes. Here we investigated this process in vivo by implanting mixed cellulose 
      ester filters or polydimethylsiloxane disks in the peritoneal cavity of wild-type 
      (WT) and monocyte chemoattractant protein-1 (MCP-1) knockout mice. We analyzed 
      classical (M1) and alternative (M2) gene expression via quantitative polymerase 
      chain reaction, immunohistochemistry and enzyme-linked immunosorbent assay in 
      both non-adherent cells isolated by lavage and implant-adherent cells. Our 
      results show that macrophages undergo unique activation that displays features of 
      both M1 and M2 polarization including induction of tumor necrosis factor alpha (TNF), 
      which induces the expression and nuclear translocation of p50 and RelA determined 
      by immunofluorescence and Western blot. Both processes were compromised in 
      fusion-deficient MCP-1 KO macrophages in vitro and in vivo. Furthermore, 
      inclusion of BAY 11-7028, an inhibitor of NFkappaB activation, reduced nuclear 
      translocation of RelA and fusion in WT macrophages. Our studies suggest that 
      peritoneal implants elicit a unique macrophage polarization phenotype leading to 
      induction of TNF and activation of the NFkappaB pathway.
CI  - Published by Elsevier Ltd.
FAU - Moore, Laura Beth
AU  - Moore LB
AD  - Department of Genetics, Yale University, New Haven, CT 06520, USA; 
      Interdepartmental Program in Vascular Biology and Therapeutics, Yale University, 
      New Haven, CT 06520, USA.
FAU - Sawyer, Andrew J
AU  - Sawyer AJ
AD  - Department of Pathology, Yale University, New Haven, CT 06520, USA; 
      Interdepartmental Program in Vascular Biology and Therapeutics, Yale University, 
      New Haven, CT 06520, USA.
FAU - Charokopos, Antonios
AU  - Charokopos A
AD  - Interdepartmental Program in Vascular Biology and Therapeutics, Yale University, 
      New Haven, CT 06520, USA.
FAU - Skokos, Eleni A
AU  - Skokos EA
AD  - Department of Pathology, Yale University, New Haven, CT 06520, USA; 
      Interdepartmental Program in Vascular Biology and Therapeutics, Yale University, 
      New Haven, CT 06520, USA.
FAU - Kyriakides, Themis R
AU  - Kyriakides TR
AD  - Department of Pathology, Yale University, New Haven, CT 06520, USA; Department of 
      Biomedical Engineering, Yale University, New Haven, CT 06520, USA; 
      Interdepartmental Program in Vascular Biology and Therapeutics, Yale University, 
      New Haven, CT 06520, USA. Electronic address: themis.kyriakides@yale.edu.
LA  - eng
GR  - GM-072194/GM/NIGMS NIH HHS/United States
GR  - T32 GM007223/GM/NIGMS NIH HHS/United States
GR  - T32 HL007950/HL/NHLBI NIH HHS/United States
GR  - 5T32HL007950-12/HL/NHLBI NIH HHS/United States
GR  - R01 GM072194/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140919
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
RN  - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Dimethylpolysiloxanes)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Nitriles)
RN  - 0 (Rela protein, mouse)
RN  - 0 (Sulfones)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (cellulose ester plastic)
RN  - 147257-52-1 (Nfkb1 protein, mouse)
RN  - 63148-62-9 (baysilon)
RN  - 9004-34-6 (Cellulose)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects/genetics
MH  - Animals
MH  - Cell Nucleus/genetics/*metabolism/pathology
MH  - Cellulose/*analogs & derivatives/toxicity
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Dimethylpolysiloxanes/*toxicity
MH  - Foreign-Body Reaction/chemically induced/genetics/*metabolism/pathology
MH  - Gene Expression Regulation/drug effects
MH  - Macrophages/*metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B p50 Subunit/genetics/*metabolism
MH  - Nitriles/pharmacology
MH  - Sulfones/pharmacology
MH  - Transcription Factor RelA/genetics/*metabolism
PMC - PMC4278755
MID - NIHMS629612
OTO - NOTNLM
OT  - Foreign body giant cell
OT  - Foreign body response
OT  - Inflammation
OT  - Macrophage
EDAT- 2014/09/23 06:00
MHDA- 2015/07/30 06:00
PMCR- 2016/01/01
CRDT- 2014/09/23 06:00
PHST- 2014/03/28 00:00 [received]
PHST- 2014/08/26 00:00 [revised]
PHST- 2014/09/11 00:00 [accepted]
PHST- 2014/09/23 06:00 [entrez]
PHST- 2014/09/23 06:00 [pubmed]
PHST- 2015/07/30 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - S1742-7061(14)00405-X [pii]
AID - 10.1016/j.actbio.2014.09.022 [doi]
PST - ppublish
SO  - Acta Biomater. 2015 Jan;11:37-47. doi: 10.1016/j.actbio.2014.09.022. Epub 2014 
      Sep 19.