科研之友
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摘要
Background-Folate receptor beta (FR beta) is induced during macrophage activation. A recombinant immunotoxin consisting of the truncated Pseudomonas exotoxin A (PE38) conjugated to an anti-FR beta antibody (anti-FR beta-PE38) has been reported to kill activated macrophages in inflammatory diseases. To elucidate the effect of an immunotoxin targeting FR beta on atherosclerosis, we determined the presence of FR beta-expressing macrophages in atherosclerotic lesions and administered the FR beta immunotoxin in apolipoprotein E-deficient mice. %26lt;br%26gt;Methods and Results-The FR beta-expressing macrophages were observed in atherosclerotic lesions of apolipoprotein E-deficient mice. At 15 or 35 weeks of age, the apolipoprotein E-deficient mice were divided into 3 groups and were intravenously administered 0.1 mg/kg of anti-FR beta-PE38 (immunotoxin group), 0.1 mg/kg of PE38 (toxin group), or 0.1 mL of saline (control group) every 3 days, for a total of 5 times for each age group. The mice were analyzed at 21 or 41 weeks of age. Treatment with the immunotoxin resulted in 31% and 22% reductions in atherosclerotic lesions of the 21- and 41-week-old mice, respectively (P%26lt;0.05). Administration of immunotoxin reduced the numbers of FR beta- and tumor necrosis factor-alpha-expressing macrophages, reduced cell proliferation, and increased the number of apoptotic cells (P%26lt;0.05). Real-time polymerase chain reaction demonstrated that the expression of FR beta and tumor necrosis factor-alpha mRNA was significantly decreased in the immunotoxin group (P%26lt;0.05). %26lt;br%26gt;Conclusions-These results suggest that FR beta-expressing macrophages exist in the atherosclerotic lesions of apolipoprotein E-deficient mice and that FR beta immunotoxin administration reduces the progression of atherosclerotic lesions in younger and older individuals. The recombinant FR beta immunotoxin targeting activated macrophages could provide a novel therapeutic tool for atherosclerosis.
- 出版日期2012-8
