ACTIVATION OF THE PHAGOCYTIC SYSTEM INCREASES INTIMAL PROLIFERATION IN HYPERCHOLESTEROLEMIC RABBITS

The effect of in vivo stimulation of the phagocytic system (neutrophil s, monocytes and hepatic Kupffer-cells) by inducing phagocytosis of in travenously administered latex particles on lipid peroxidation and aor tic intimal proliferation was tested in cholesterol-fed rabbits. Three weeks after starting the diet, aortic intimal proliferation was measu red by the intimal to medial ratios and by the incorporation of [H-3]t hymidine, infused into the circulation for the preceding 14 days. Inti mal to medial ratios were increased (0.473 +/- 0.023 vs. 0.282 +/- 0.0 11, P < 0.01) and aortic [H-3]thymidine contents were higher (66.8 +/- 3.5 vs. 27.8 +/- 49 counts/min per mg, P = 0.0001) in latex bead-trea ted than in control animals. Injection of beads transiently increased plasma lipid peroxide levels. At the end of the 3 week experiment, pla sma lipid peroxide levels were still elevated and lipid peroxide conte nts of the aortic walls were higher in the latex-treated rabbits(82.8 +/- 5.8 vs. 46.4 +/- 4.9 nmol/mg cholesterol, latex-treated vs. contro ls, P = 0.004). These data suggest a significant acceleration of ather ogenesis by the stimulated phagocytic system, the mechanism of which m ay involve lipid peroxidation.