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 patho genesis of atherosclerosis. This recruitment is interpreted as enhanci ng lesion development, but it could also be a host response limiting l ipid accumulation. The ability of macrophages to limit cholesterol upt ake, however, can be reduced by the impaired mobility and metabolic ac tivity associated with foam cell development. As lesions enlarge, foam cells die and become the nidus for the necrotic core. Treatments to i mprove viability might improve foam cell function and promote regressi on. Macrophage colony-stimulating factor (M-CSF) is vital to monocyte/ macrophage differentiation, proliferation, and activation. We found th at 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 reduce d cholesterol content of these foam cells. (C) 1997 Wiley-Liss, Inc.