Effects of monocyte macrophages stimulation on hepatic lipoprotein receptors.

The first series of in vivo experiments were designed to investigate the effects of monocytic macrophages (MM phi) stimulation by zymosan in cholesterol-fed rats. We found that the MM phi stimulation significantly decreased plasma very-low-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol but not high-density lipoprotein-cholesterol. The hepatic and aortic cholesterol levels were also significantly decreased; meanwhile, the biliary total bile acid and fecal sterol excretion were significantly enhanced. These results were beneficial to the prevention and regression of atherosclerosis. The second series of in vitro experiments led to the discovery that zymosan did not have effect on HDL and LDL binding, uptake and degradation of hepatic parenchymal and nonparenchymal cells isolated from normal rats, but did have significant effects on those isolated from cholesterol-fed rats. The experiments of Kupffer cells modulating hepatocytes also demonstrated that hepatocyte HDL receptor activity was significantly enhanced by conditioned medium from acetylated LDL plus zymosan added to Kupffer cells. Bmax of 125I-labeled HDL specific binding was increased from 237.8 to 295.2 ng/mg cell protein. The Ka value was not affected, indicating that there might be an increment in receptor number, but not receptor affinity. Cholesterol-loaded zymosan-stimulated Kupffer cells might secrete a soluble mediator affecting hepatocyte HDL receptor activity. Zymosan and other MM phi-stimulating reagents are promising in the exploration of a new approach for prevention and treatment of hypercholesterolemia and atherosclerosis.