Detection of monocyte chemoattractant protein-1 receptor expression in experimental atherosclerotic lesions: An autoradiographic study

Abstract

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 125I-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). 125I-MCP-1 has a blood clearance half-time of ≈ 10 minutes and circulates in association with cells. The liver, lungs, and kidneys had the highest concentration of 125I-MCP-1 at 5 and 30 minutes after tracer administration. Autoradiograms revealed accumulation of 125I-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 125I-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 125I-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.