PMID- 21514443
OWN - NLM
STAT- MEDLINE
DCOM- 20110826
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 178
IP  - 5
DP  - 2011 May
TI  - Lack of TNF-alpha-induced MMP-9 production and abnormal E-cadherin redistribution 
      associated with compromised fusion in MCP-1-null macrophages.
PG  - 2311-21
LID - 10.1016/j.ajpath.2011.01.045 [doi]
AB  - Homotypic cell fusion occurs in several cell types including macrophages in the 
      formation of foreign body giant cells. Previously, monocyte chemoattractant 
      protein-1 (MCP-1) was demonstrated to be required for foreign body giant cell 
      formation in the foreign body response. The present study investigated the fusion 
      defect in MCP-1-null macrophages by implanting biomaterials intraperitoneally in 
      wild-type and MCP-1-null mice and monitoring the macrophage response at 12 hours 
      to 4 weeks. MCP-1-null mice exhibited reduced accumulation and fusion of 
      macrophages on implants, which was associated with attenuation of the foreign 
      body response. Consistent with previous in vitro findings, the level of matrix 
      metalloproteinase-9 (MMP-9) was reduced in MCP-1-null macrophages adherent to 
      implants. In contrast, CCR2 expression was unaffected. In vitro studies revealed 
      reduced tumor necrosis factor-alpha (TNF-alpha) production and abnormal subcellular 
      redistribution of E-cadherin and beta-catenin during fusion in MCP-1-null 
      macrophages. Exogenous TNF-alpha caused an increase in the production of MMP-9 and 
      rescued the fusion defect. Addition of GM6001 (MMP inhibitor) or NSC23766 (Rac1 
      inhibitor) indicated two distinct induction pathways, one for 
      E-cadherin/beta-catenin and one for MCP-1, TNF-alpha, and MMP-9. Considered together, 
      these observations demonstrate that induction of E-cadherin/beta-catenin is not 
      sufficient for fusion in the absence of MCP-1 or the downstream mediators TNF-alpha 
      and MMP-9. Moreover, attenuation of the foreign body response in intraperitoneal 
      implants in MCP-1-null mice demonstrates that the process depends on 
      tissue-specific factors.
CI  - Copyright (c) 2011 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Skokos, Eleni A
AU  - Skokos EA
AD  - Department of Pathology, Yale University School of Medicine, New Haven, 
      Connecticut, USA.
FAU - Charokopos, Antonios
AU  - Charokopos A
FAU - Khan, Khadija
AU  - Khan K
FAU - Wanjala, Jackie
AU  - Wanjala J
FAU - Kyriakides, Themis R
AU  - Kyriakides TR
LA  - eng
GR  - R01 GM072194/GM/NIGMS NIH HHS/United States
GR  - GM072194-01/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Cadherins)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cadherins/*metabolism
MH  - Cell Adhesion/physiology
MH  - Chemokine CCL2/*metabolism
MH  - Chemotaxis, Leukocyte/physiology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Giant Cells, Foreign-Body/*metabolism
MH  - Immunohistochemistry
MH  - Macrophages/metabolism
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Microscopy, Electron, Transmission
MH  - Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC3081180
EDAT- 2011/04/26 06:00
MHDA- 2011/08/30 06:00
PMCR- 2012/05/01
CRDT- 2011/04/26 06:00
PHST- 2010/08/06 00:00 [received]
PHST- 2010/12/15 00:00 [revised]
PHST- 2011/01/18 00:00 [accepted]
PHST- 2011/04/26 06:00 [entrez]
PHST- 2011/04/26 06:00 [pubmed]
PHST- 2011/08/30 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - S0002-9440(11)00161-1 [pii]
AID - AJPA272 [pii]
AID - 10.1016/j.ajpath.2011.01.045 [doi]
PST - ppublish
SO  - Am J Pathol. 2011 May;178(5):2311-21. doi: 10.1016/j.ajpath.2011.01.045.