MONOCYTE-MACROPHAGE PROCOAGULANT ACTIVITY AND ENDOTHELIAL THROMBOMODULIN IN RABBITS FED AN ATHEROGENIC DIET

Abstract

Mononuclear phagocytes (M) and vascular cellsmay participate in the events that lead tothe development of atherosclerotic lesions. We have studied the procoagulant activity (PCA) of M and thrombomodulin (TM)-like activityofendothelial cells in 15 rabbits fed an atherogenic diet for 4-5 weeks and in 15 rabbits fed a standard diet. Peripheral blood and spleen M were tested for PCA immediately after isolation (basal PCA) and following in vitro stimulation by bacterial endotoxin, using a one-stage clotting assay. TM-like activity was measured by the rate of (bovine) protein C activation induced by catalytic concentrations of thrombin in the presence of aortic rings (1cm long) and CaCl2 Blood M expressed negligible basal PCA (< 1 U/105 M) both in hyperlipaemic and controlrabbits. Endotoxin-induced PCA was not significantly different in the two groups. In contrast, dietary treatment resulted in a significant increase in the basal PCA of spleen M (67.6 ± 13.5 vs 26.5 ± 5.4 U/105 M, pcO.Ol). Moreover, spleen M fromtreated animals produced significantly more PCA than controls (p<0.01) in response to endotoxin. When rabbits were given a single injection of endotoxin, spleen M harvested 60 min after the injection from hyperlipaemicanimals expressed 3 times more PCA (p<0.05, n=6) than did cells from controls. In all instances PCA was identified as tissue factor. TM activity associated with the endothelium was not different in the two groups of animals notwithstanding the presence of fatty streaks on the aortic endothelium of treated rabbits. It is suggested that dietary fats maycause early functional changes in M that leadto increased PCA production both in vivo and in vitro.These data may be relevant to an understanding of the role of M in the pathogenesis of atherosclerosis.