ENHANCED LDL OXIDATION BY MURINE MACROPHAGE FOAM CELLS AND THEIR FAILURE TO SECRETE NITRIC-OXIDE

Foam cells were produced in vitro by incubation of mouse peritoneal ma crophages with acetylated or copper-oxidized LDL. Nitric oxide synthes is was stimulated by exposure of the cells to IFN gamma and LPS. Nitri c oxide production, detected by measurement of nitrite in the culture medium, was unchanged in Ac-LDL loaded cells as compared with non-load ed cells. However, Ox-LDL foam cells produced 68-99%, less nitrite tha n non-loaded cells. Failure to detect nitric oxide synthase (NOS) prod ucts from macrophages previously loaded with Ox-LDL appeared to result from lack of NOS activity, as little active enzyme could be recovered from Ox-LDL loaded cells. However, addition of Ox-LDL to an active ce ll-free NOS preparation had no direct effect on enzymic activity. When native LDL was subsequently incubated with these various IFN gamma/LP S stimulated cells, cells pre-loaded with Ox-LDL promoted, on average, a 2-fold greater increase in oxidative modification of the LDL added than either non-loaded or Ac-LDL loaded cells. That is, there was an i nverse correlation between NOS activity and the ability of the cells t o promote LDL oxidation. Unstimulated Ox-LDL loaded foam cells also ox idized LDL better than unstimulated non-loaded or Ac-LDL loaded foam c ells, and the extent of oxidative modification was generally greater t han seen with the equivalent IFN gamma/LPS stimulated cells. This sugg ests that Ox-LDL loading also affects some additional factor(s) respon sible for cell-mediated LDL oxidation.