Detection of monocyte chemoattractant protein-1 receptor expression in experimental atherosclerotic lesions: an autoradiographic study.
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.
Ohtsuki
K
K
Division of Nuclear Medicine, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
Hayase
M
M
Akashi
K
K
Kopiwoda
S
S
Strauss
H W
HW
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D001345:Autoradiography; D018932:Chemokine CCL2 / Q000378:metabolism / Q000493:pharmacokinetics*; D004396:Coloring Agents; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005070:Evans Blue; D007083:Iliac Artery / Q000378:metabolism / Q000473:pathology; D007457:Iodine Radioisotopes; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D014018:Tissue Distribution; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D017540:Tunica Media / Q000378:metabolism / Q000473:pathology
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D004396:Coloring Agents; D007457:Iodine Radioisotopes; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D005070:Evans Blue