Document Detail

Detection of monocyte chemoattractant protein-1 receptor expression in experimental atherosclerotic lesions: an autoradiographic study.
MedLine Citation:
PMID:  11447087     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Monocytes, a common component of atheroma, are attracted to the lesion site in response to chemotactic signals, particularly expression of monocyte chemoattractant peptide 1 (MCP-1). This study assessed the feasibility of using radiolabeled MCP-1 to identify monocytes and macrophages that have localized at sites of experimental arterial lesions. Methods and Results-- The biodistribution of radiolabeled MCP-1 was determined in normal mice, and localization in experimental atheroma was determined in cholesterol-fed rabbits 4 weeks after arterial injury of the iliac artery (9 rabbits) and the abdominal aorta (1 rabbit). Vessels were harvested and autoradiographed after intravenous administration of (125)I-labeled MCP-1 and Evans blue dye. The arteries were evaluated histologically by hematoxylin and eosin staining and immune staining with a monoclonal antibody specific for rabbit macrophages (RAM-11). (125)I-MCP-1 has a blood clearance half-time of approximately 10 minutes and circulates in association with cells. The liver, lungs, and kidneys had the highest concentration of (125)I-MCP-1 at 5 and 30 minutes after tracer administration. Autoradiograms revealed accumulation of (125)I-MCP-1 in the damaged artery wall, with an average ratio of lesion to normal vessel of 6:1 (maximum 45:1). The accumulation of (125)I-MCP-1 in the reendothelialized (plaque formation) areas was greater than in the deendothelialized (Evans blue-positive) areas (6.55+/-2.26 versus 4.34+/-1.43 counts/pixel, P<0.05). The uptake of (125)I-MCP-1 correlated with the number of macrophages per unit area (r=0.85, P<0.0001).
CONCLUSIONS: Radiolabeled MCP-1 may be a useful tracer for imaging monocyte/macrophage-rich experimental atherosclerotic lesions.
K Ohtsuki; M Hayase; K Akashi; S Kopiwoda; H W Strauss
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  104     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-07-11     Completed Date:  2001-08-09     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  203-8     Citation Subset:  AIM; IM    
Division of Nuclear Medicine, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
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MeSH Terms
Aorta, Abdominal / metabolism,  pathology
Arteriosclerosis / metabolism*,  pathology
Chemokine CCL2 / metabolism,  pharmacokinetics*
Coloring Agents
Diet, Atherogenic
Disease Models, Animal
Evans Blue
Iliac Artery / metabolism,  pathology
Iodine Radioisotopes
Macrophages / metabolism,  pathology
Metabolic Clearance Rate / physiology
Mice, Inbred BALB C
Monocytes / metabolism,  pathology
Receptors, CCR2
Receptors, Chemokine / biosynthesis*
Tissue Distribution
Tunica Intima / metabolism,  pathology
Tunica Media / metabolism,  pathology
Reg. No./Substance:
0/Ccr2 protein, mouse; 0/Chemokine CCL2; 0/Coloring Agents; 0/Iodine Radioisotopes; 0/Receptors, CCR2; 0/Receptors, Chemokine; 314-13-6/Evans Blue

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