Immunoreactive macrophage colony-stimulating factor is increased in atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits after recombinant human macrophage colony-stimulating factor therapy.
Infiltration of monocytes into arteries is an early event in the pathogenesis of atherosclerosis. This recruitment is interpreted as enhancing lesion development, but it could also be a host response limiting lipid accumulation. The ability of macrophages to limit cholesterol uptake, however, can be reduced by the impaired mobility and metabolic activity associated with foam cell development. As lesions enlarge, foam cells die and become the nidus for the necrotic core. Treatments to improve viability might improve foam cell function and promote regression. Macrophage colony-stimulating factor (M-CSF) is vital to monocyte/macrophage differentiation, proliferation, and activation. We found that foam cells of Watanabe heritable hyperlipidemic (WHHL) rabbits had faint staining for M-CSF. Treatment of rabbits with recombinant human M-CSF (rhM-CSF) increased M-CSF staining, which correlated with reduced cholesterol content of these foam cells.
Donnelly
L H
LH
Department of Preclinical Research and Development, Genetics Institute, Inc., Cambridge, Massachusetts 02140, USA.
Bree
M P
MP
Hunter
S E
SE
Keith
J C
JC
Schaub
R G
RG
D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001018:Aortic Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use; D008297:Male; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D002784:Cholesterol