EFFECTS OF DEXAMETHASONE ON MIGRATION OF HUMAN MONOCYTES IN RESPONSE TO OXIDIZED BETA-VERY LOW-DENSITY-LIPOPROTEIN

Objective: We previously showed that dexamethasone inhibited the devel opment of atherosclerosis in cholesterol-fed rabbits. In the present s tudy, we investigated the mechanisms of this inhibition. Methods: Mono cytes were isolated from the peripheral blood of healthy donors. Cell suspensions were incubated with dexamethasone, 10(-11)-10(-4)M, for 90 minutes at 37 degrees C. Rabbit beta-very low density lipoprotein(bet a-VLDL) was obtained from New Zealand White rabbits that had been fed chow containing 1% cholesterol. Oxidative modification of beta-VLDL wa s performed by autooxidation. We measured the migration of monocytes i n response to native and oxidized beta-VLDL using a 48-well microchemo taxis chamber. Results: Oxidized beta-VLDL stimulated the migration of monocytes dose-dependently in the range between 0.5 and 2 nmol/mg pro tein. Dexamethasone inhibited the chemotaxis of monocytes exposed to o xidized beta-VLDL in a dose-dependent manner more than 10(-9)M. Conclu sions: Inhibition of the chemotactic response of monocytes exposed to oxidized beta-VLDL may be a mechanism for the anti-atherogenic effect of dexamethasone in cholesterol-fed rabbits.