Intraperitoneal administration of anti-c-fms monoclonal antibody prevents initial events of atherogenesis but does not reduce the size of advanced lesions in apolipoprotein E-deficient mice.
BACKGROUND
Atherosclerosis results from complex inflammatory-fibroproliferative responses. To elucidate the central role of macrophage and macrophage-colony stimulating factor (M-CSF) during atherogenesis, we used a new strategy to administer to adult apolipoprotein E (apoE)-deficient mice a monoclonal antibody (AFS98) raised against c-fms, the receptor of M-CSF.


RESULTS
When 6-week-old apoE-deficient mice were fed a high-fat diet and injected with 2 mg of AFS98 intraperitoneally on alternate days for 6 weeks, accumulation of macrophage-derived foam cells in the aortic root was suppressed by 70% compared with that in controls. This preventive effect was associated with neither remarkable decrease of the number of circulating monocytes nor systemic growth retardation. In contrast, when apoE-deficient mice that had been fed a high-fat diet from 6 weeks of age were given AFS98 from 12 to 18 weeks of age, a minimal protective effect on lesion size was observed.


CONCLUSIONS
These results suggest that (1) macrophage and M-CSF/c-fms play an essential role in the arterial wall during development of the fatty streak lesion and (2) blockade of the M-CSF/c-fms pathway could act as protection from at least early atherogenesis but could have a less preventive effect on maintenance of the advanced lesions.
Murayama
T
T
Departments of Geriatric Medicine, and Molecular Genetics, Graduate School of Medicine, Kyoto University, Japan.
Yokode
M
M
Kataoka
H
H
Imabayashi
T
T
Yoshida
H
H
Sano
H
H
Nishikawa
S
S
Nishikawa
S
S
Kita
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001011:Aorta / Q000473:pathology*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D005260:Female; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000166:cytology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D016186:Receptor, Macrophage Colony-Stimulating Factor