PMID- 24632850
OWN - NLM
STAT- MEDLINE
DCOM- 20141118
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 3
DP  - 2014
TI  - Monocyte chemoattractant protein-1 (MCP-1) regulates macrophage cytotoxicity in 
      abdominal aortic aneurysm.
PG  - e92053
LID - 10.1371/journal.pone.0092053 [doi]
LID - e92053
AB  - AIMS: In abdominal aortic aneurysm (AAA), macrophages are detected in the 
      proximity of aortic smooth muscle cells (SMCs). We have previously demonstrated 
      in a murine model of AAA that apoptotic SMCs attract monocytes and other 
      leukocytes by producing MCP-1. Here we tested whether infiltrating macrophages 
      also directly contribute to SMC apoptosis. METHODS AND RESULTS: Using a 
      SMC/RAW264.7 macrophage co-culture system, we demonstrated that MCP-1-primed RAWs 
      caused a significantly higher level of apoptosis in SMCs as compared to control 
      macrophages. Next, we detected an enhanced Fas ligand (FasL) mRNA level and 
      membrane FasL protein expression in MCP-1-primed RAWs. Neutralizing FasL blocked 
      SMC apoptosis in the co-culture. In situ proximity ligation assay showed that 
      SMCs exposed to primed macrophages contained higher levels of receptor 
      interacting protein-1 (RIP1)/Caspase 8 containing cell death complexes. Silencing 
      RIP1 conferred apoptosis resistance to SMCs. In the mouse elastase injury model 
      of aneurysm, aneurysm induction increased the level of RIP1/Caspase 8 containing 
      complexes in medial SMCs. Moreover, TUNEL-positive SMCs in aneurysmal tissues 
      were frequently surrounded by CD68(+)/FasL(+) macrophages. Conversely, 
      elastase-treated arteries from MCP-1 knockout mice display a reduction of both 
      macrophage infiltration and FasL expression, which was accompanied by diminished 
      apoptosis of SMCs. CONCLUSION: Our data suggest that MCP-1-primed macrophages are 
      more cytotoxic. MCP-1 appears to modulate macrophage cytotoxicity by increasing 
      the level of membrane bound FasL. Thus, we showed that MCP-1-primed macrophages 
      kill SMCs through a FasL/Fas-Caspase8-RIP1 mediated mechanism.
FAU - Wang, Qiwei
AU  - Wang Q
AD  - Division of Vascular Surgery, Department of Surgery, University of 
      Wisconsin-Madison, Wisconsin, United States of America.
FAU - Ren, Jun
AU  - Ren J
AD  - Division of Vascular Surgery, Department of Surgery, University of 
      Wisconsin-Madison, Wisconsin, United States of America.
FAU - Morgan, Stephanie
AU  - Morgan S
AD  - Division of Vascular Surgery, Department of Surgery, University of 
      Wisconsin-Madison, Wisconsin, United States of America.
FAU - Liu, Zhenjie
AU  - Liu Z
AD  - Division of Vascular Surgery, Department of Surgery, University of 
      Wisconsin-Madison, Wisconsin, United States of America.
FAU - Dou, Changlin
AU  - Dou C
AD  - Luye Pharma Group, Yantai, China.
FAU - Liu, Bo
AU  - Liu B
AD  - Division of Vascular Surgery, Department of Surgery, University of 
      Wisconsin-Madison, Wisconsin, United States of America.
LA  - eng
GR  - T32 HL007936/HL/NHLBI NIH HHS/United States
GR  - T32 HL 07936/HL/NHLBI NIH HHS/United States
GR  - R01 HL088447/HL/NHLBI NIH HHS/United States
GR  - T32 HL110853/HL/NHLBI NIH HHS/United States
GR  - R01HL088447/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140314
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Ralbp1 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Animals
MH  - Aortic Aneurysm, Abdominal/*immunology/*metabolism/pathology
MH  - Apoptosis
MH  - Caspase 3/metabolism
MH  - Caspase 8/metabolism
MH  - Cell Line
MH  - Chemokine CCL2/*metabolism
MH  - Coculture Techniques
MH  - Fas Ligand Protein/metabolism
MH  - GTPase-Activating Proteins/metabolism
MH  - Gene Expression Regulation
MH  - Macrophages/*cytology/immunology/*metabolism
MH  - Male
MH  - Mice
MH  - Myocytes, Smooth Muscle/pathology
PMC - PMC3954911
COIS- Competing Interests: CD was an employee of Luye Pharma at the time of the study. 
      There are no patents, products in development or marketed products to declare. 
      This does not alter the authors' adherence to all the PLOS ONE policies on 
      sharing data and materials.
EDAT- 2014/03/19 06:00
MHDA- 2014/11/19 06:00
PMCR- 2014/03/14
CRDT- 2014/03/18 06:00
PHST- 2013/10/22 00:00 [received]
PHST- 2014/02/17 00:00 [accepted]
PHST- 2014/03/18 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2014/11/19 06:00 [medline]
PHST- 2014/03/14 00:00 [pmc-release]
AID - PONE-D-13-43085 [pii]
AID - 10.1371/journal.pone.0092053 [doi]
PST - epublish
SO  - PLoS One. 2014 Mar 14;9(3):e92053. doi: 10.1371/journal.pone.0092053. eCollection 
      2014.