PMID- 19404946
OWN - NLM
STAT- MEDLINE
DCOM- 20090630
LR  - 20211020
IS  - 0004-3591 (Print)
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 60
IP  - 5
DP  - 2009 May
TI  - Induction of CCR2-dependent macrophage accumulation by oxidized phospholipids in 
      the air-pouch model of inflammation.
PG  - 1362-71
LID - 10.1002/art.24448 [doi]
AB  - OBJECTIVE: Macrophages are key players in the pathogenesis of rheumatoid 
      synovitis as well as in atherosclerosis. To determine whether atherogenic 
      oxidized phospholipids potentially contribute to synovial inflammation and 
      subsequent monocyte/macrophage recruitment, we examined the effects of oxidized 
      1- palmitoyl-2-arachidonoyl-sn-3-glycero-phosphorylcholine (OxPAPC) on chemokine 
      expression and leukocyte recruitment in a facsimile synovium in vivo using the 
      murine air-pouch model. METHODS: Air pouches were raised by 2 injections of 
      sterile air, and inflammation was induced by injecting either lipopolysaccharide 
      (LPS) or OxPAPC into the pouch lumen. Inflammation was assessed by analysis of 
      inflammatory gene expression using reverse transcription-polymerase chain 
      reaction or immunohistochemical analysis, and leukocytes were quantified in the 
      lavage fluid and in the pouch wall after staining with Giemsa or after enzymatic 
      digestion followed by fluorescence-activated cell sorter analysis. RESULTS: 
      Application of OxPAPC resulted in selective recruitment of monocyte/macrophages 
      into the air-pouch wall, but not in the lumen. In contrast, LPS induced both 
      monocyte and neutrophil accumulation in the pouch lumen as well as in the wall. 
      LPS, but not OxPAPC, induced the expression of adhesion molecules E-selectin, 
      P-selectin, intercellular adhesion molecule 1, and vascular cell adhesion 
      molecule 1. OxPAPC increased the expression of the CCR2 ligands monocyte 
      chemotactic protein 1 (MCP-1), MCP-3, and MCP-5, as well as RANTES and 
      growth-related oncogene alpha (GROalpha), while it down-regulated the expression 
      of CCR2 on macrophages. Moreover, oxidized phospholipid-induced macrophage 
      accumulation was abrogated in CCR2-/- mice. CONCLUSION: These data demonstrate 
      that oxidized phospholipids trigger a type of inflammatory response that leads to 
      selective macrophage accumulation in vivo, a process relevant for the 
      pathogenesis of chronic inflammatory rheumatic diseases.
FAU - Kadl, Alexandra
AU  - Kadl A
AD  - Robert M. Berne Cardiovascular Research Center, University of Virginia, 
      Charlottesville, VA 22908, USA.
FAU - Galkina, Elena
AU  - Galkina E
FAU - Leitinger, Norbert
AU  - Leitinger N
LA  - eng
GR  - R01-HL-084422-01/HL/NHLBI NIH HHS/United States
GR  - R01 HL084422-01/HL/NHLBI NIH HHS/United States
GR  - R01 HL084422-02/HL/NHLBI NIH HHS/United States
GR  - R01 HL084422-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL084422/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (CCR2 protein, human)
RN  - 0 (Ccl12 protein, mouse)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (E-Selectin)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Monocyte Chemoattractant Proteins)
RN  - 0 (P-Selectin)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0 (oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 3.4.17.1 (Carboxypeptidases A)
RN  - EC 3.4.17.1 (Cpa3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Carboxypeptidases A/analysis
MH  - Chemokine CCL2/analysis
MH  - Chemokine CCL5/analysis
MH  - Chemokine CXCL1/analysis
MH  - E-Selectin/analysis
MH  - Female
MH  - Histological Techniques
MH  - Inflammation/*physiopathology
MH  - Intercellular Adhesion Molecule-1/analysis
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monocyte Chemoattractant Proteins/analysis
MH  - Monocytes/physiology
MH  - Neutrophils/physiology
MH  - P-Selectin/analysis
MH  - Phosphatidylcholines/*pharmacology
MH  - Receptors, CCR2/*physiology
MH  - Rheumatic Diseases/physiopathology
MH  - Synovial Membrane/physiology
MH  - Vascular Cell Adhesion Molecule-1/analysis
PMC - PMC2745196
MID - NIHMS131904
EDAT- 2009/05/01 09:00
MHDA- 2009/07/01 09:00
PMCR- 2009/09/16
CRDT- 2009/05/01 09:00
PHST- 2009/05/01 09:00 [entrez]
PHST- 2009/05/01 09:00 [pubmed]
PHST- 2009/07/01 09:00 [medline]
PHST- 2009/09/16 00:00 [pmc-release]
AID - 10.1002/art.24448 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2009 May;60(5):1362-71. doi: 10.1002/art.24448.