K. Ohtsuki et al., Detection of monocyte chemoattractant protein-1 receptor expression in experimental atherosclerotic lesions - An autoradiographic study, CIRCULATION, 104(2), 2001, pp. 203-208
Citations number
35
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
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 feasibi
lity 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 determine
d in normal mice, and localization in experimental atheroma was determined
in cholesterol-fed rabbits 4 weeks after arterial injury of the iliac arter
y (9 rabbits) and the abdominal aorta (1 rabbit). Vessels were harvested an
d autoradiographed after intravenous administration of I-125-labeled MCP-1
and Evans blue dye. The arteries were evaluated histologically by hematoxyl
in and eosin staining and immune staining with a monoclonal antibody specif
ic for rabbit macrophages (RAM-11). I-125-MCP-1 has a blood clearance half-
time of approximate to 10 minutes and circulates in association with cells.
The liver, lungs, and kidneys had the highest concentration of I-125-MCP-1
at 5 and 30 minutes after tracer administration, Autoradiograms revealed a
ccumulation of I-125-MCP-1 in the damaged artery wall, with an average rati
o of lesion to normal vessel of 6:1 (maximum 45:1). The accumulation of I-1
25-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 I-125-MCP-1 correlated w
ith 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.