PMID- 9848893
OWN - NLM
STAT- MEDLINE
DCOM- 19990107
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 18
IP  - 12
DP  - 1998 Dec
TI  - Chemokine receptor CCR2 expression and monocyte chemoattractant 
      protein-1-mediated chemotaxis in human monocytes. A regulatory role for plasma 
      LDL.
PG  - 1983-91
AB  - The subendothelial accumulation of macrophage-derived foam cells is one of the 
      hallmarks of atherosclerosis. The recruitment of monocytes to the intima requires 
      the interaction of locally produced chemokines with specific cell surface 
      receptors, including the receptor (CCR2) for monocyte chemoattractant protein-1 
      (MCP-1). We have previously reported that monocyte CCR2 gene expression and 
      function are effectively downregulated by proinflammatory cytokines. In this 
      study we identified low density lipoprotein (LDL) as a positive regulator of CCR2 
      expression. Monocyte CCR2 expression was dramatically increased in 
      hypercholesterolemic patients compared with normocholesterolemic controls. 
      Similarly, incubation of human THP-1 monocytes with LDL induced a rapid increase 
      in CCR2 mRNA and protein. By 24 hours the number of cell surface receptors was 
      doubled, causing a 3-fold increase in the chemotactic response to MCP-1. The 
      increase in CCR2 expression and chemotaxis was promoted by native LDL but not by 
      oxidized LDL. Oxidized LDL rapidly downregulated CCR2 expression, whereas 
      reductively methylated LDL, which does not bind to the LDL receptor, had only 
      modest effects on CCR2 expression. A neutralizing anti-LDL receptor antibody 
      prevented the effect of LDL, suggesting that binding and internalization of LDL 
      were essential for CCR2 upregulation. The induction of CCR2 expression appeared 
      to be mediated by LDL-derived cholesterol, because cells treated with free 
      cholesterol also showed increased CCR2 expression. These data suggest that 
      elevated plasma LDL levels in conditions such as hypercholesterolemia enhance 
      monocyte CCR2 expression and chemotactic response and potentially contribute to 
      increased monocyte recruitment to the vessel wall in chronic inflammation and 
      atherogenesis.
FAU - Han, K H
AU  - Han KH
AD  - Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
FAU - Tangirala, R K
AU  - Tangirala RK
FAU - Green, S R
AU  - Green SR
FAU - Quehenberger, O
AU  - Quehenberger O
LA  - eng
GR  - HL56989/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Receptors, Cytokine)
RN  - 0 (Receptors, LDL)
RN  - 0 (oxidized low density lipoprotein)
SB  - IM
MH  - Aged
MH  - Arteriosclerosis/blood
MH  - Cells, Cultured
MH  - Chemokine CCL2/*physiology
MH  - *Chemotaxis, Leukocyte
MH  - Female
MH  - Humans
MH  - Lipoproteins, LDL/blood/*physiology
MH  - Middle Aged
MH  - Monocytes/*physiology
MH  - RNA, Messenger/analysis
MH  - Receptors, CCR2
MH  - *Receptors, Chemokine
MH  - Receptors, Cytokine/*analysis/genetics
MH  - Receptors, LDL/physiology
EDAT- 1998/12/16 00:00
MHDA- 1998/12/16 00:01
CRDT- 1998/12/16 00:00
PHST- 1998/12/16 00:00 [pubmed]
PHST- 1998/12/16 00:01 [medline]
PHST- 1998/12/16 00:00 [entrez]
AID - 10.1161/01.atv.18.12.1983 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 1998 Dec;18(12):1983-91. doi: 
      10.1161/01.atv.18.12.1983.